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Clinical MedicineIn-Press PreviewClinical trialsImmunology Open Access | 10.1172/JCI161400

Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-b blockade in HPV-unrelated head and neck cancer

Jason M. Redman,1 Jay Friedman,2 Yvette Robbins,2 Cem Sievers,2 Xinping Yang,2 Wiem Lassoued,4 Andrew Sinkoe,1 Antonios Papanicolau-Sengos,5 Chyi-Chia R. Lee,5 Jennifer L. Marte,6 Evrim B. Turkbey,7 Wojciech Mydlarz,8 Arjun S. Joshi,9 Nyall R. London, Jr.,8 Matthew Pierce,10 Rodney J. Taylor,11 Steven Hong,12 Andrew Nguyen,13 Patrick Soon-Shiong,14 Jeffrey Schlom,15 James L. Gulley,16 and Clint T. Allen2

1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

Find articles by Gulley, J. in: JCI | PubMed | Google Scholar |

1Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

2Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Bethesda, United States of America

3Section on Translational Tumor Immunology, National Institute on Deafness a, NIH, Rockville, United States of America

4Tumor Immune Microenvironment Laboratory, Genitourinary Malignancy Branch, NCI, CCR. NIH, Bethesda, United States of America

5Laboratory of Pathology, CCR, NCI, NIH, Bethesda, United States of America

6Genitourinary Malignancies Branch, NCI, CCR. NIH, Bethesda, United States of America

7Radiology and Imaging Sciences, NIH, Bethedsda, United States of America

8Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States of America

9Department of Surgery, George Washington University, Washington, DC, United States of America

10Department of Otolaryngology-Head and Neck Surgery, Georgetown University School of Medicine, Washington, DC, United States of America

11Department of Otolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, United States of America

12Department of Otolaryngology-Head and Neck Surgery, Walter Reed Army Medical Center, Bethesda, United States of America

13ImmunityBio, Culver City, United States of America

14Advanced Health, ImmunityBio, Culver City, United States of America

15Laboratory of Tumor Immunology and Biology, NCI, CCR, NIH, Bethesda, United States of America

16Genitourinary Malignancy Branch, NCI, CCR, NIH, Bethesda, United States of America

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Published June 21, 2022 - More info

J Clin Invest. https://doi.org/10.1172/JCI161400.
Copyright © 2022, Redman et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 21, 2022 - Version history
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Abstract

Background: Head and neck squamous cell carcinoma not associated with human papillomavirus (HPV-unrelated HNSCC) is associated with high rates of recurrence and poor survival. Methods: We conducted a clinical trial in 14 patients with newly diagnosed, HPV-unrelated HNSCC to evaluate the safety and efficacy of neoadjuvant bintrafusp alfa, a bifunctional fusion protein that blocks programmed death-ligand 1 (PD-L1) and neutralizes transforming growth factor-beta (TGF-). Results: Bintrafusp alfa was well tolerated, and no treatment-associated surgical delays or complications occurred. Objective pathologic responses were observed and 12 of 14 patients (86%) were alive and disease free at one year. Alterations in regulatory T cell infiltration and spatial distribution relative to proliferating CD8 T cells indicated reversal of Treg immunosuppression in the primary tumor. Detection of neoepitope-specific tumor T cell responses, but not viral-specific responses, correlated with development of a pathologic response. Detection of neoepitope-specific responses and pathologic responses in tumors was not correlated with genomic features or tumor antigenicity but was associated with reduced pre-treatment myeloid cell tumor infiltration. These results indicate that dual PD-L1 and TGF- blockade can safely enhance tumor antigen-specific immunity and highlight the feasibility of multi-mechanism neoadjuvant immunotherapy in patients with HPV-unrelated HNSCC. Conclusion: Our studies provide new insight into the ability of neoadjuvant immunotherapy to induce polyclonal neoadjuvant-specific T cell responses in tumors and suggest that features of the tumor microenvironment, such as myeloid cell infiltration, may be a major determinant of enhanced anti-tumor immunity following such treatment.

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  • Version 1 (June 21, 2022): In-Press Preview
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