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Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance
Dhanya K. Nambiar, … , Amato Giaccia, Quynh Thu Le
Dhanya K. Nambiar, … , Amato Giaccia, Quynh Thu Le
Published November 11, 2019
Citation Information: J Clin Invest. 2019;129(12):5553-5567. https://doi.org/10.1172/JCI129025.
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Research Article Oncology

Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance

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Abstract

Immune checkpoint inhibitors (ICIs), although promising, have variable benefit in head and neck cancer (HNC). We noted that tumor galectin-1 (Gal1) levels were inversely correlated with treatment response and survival in patients with HNC who were treated with ICIs. Using multiple HNC mouse models, we show that tumor-secreted Gal1 mediates immune evasion by preventing T cell migration into the tumor. Mechanistically, Gal1 reprograms the tumor endothelium to upregulate cell-surface programmed death ligand 1 (PD-L1) and galectin-9. Using genetic and pharmacological approaches, we show that Gal1 blockade increases intratumoral T cell infiltration, leading to a better response to anti-PD1 therapy with or without radiotherapy. Our study reveals the function of Gal1 in transforming the tumor endothelium into an immune-suppressive barrier and that its inhibition synergizes with ICIs.

Authors

Dhanya K. Nambiar, Todd Aguilera, Hongbin Cao, Shirley Kwok, Christina Kong, Joshua Bloomstein, Zemin Wang, Vangipuram S. Rangan, Dadi Jiang, Rie von Eyben, Rachel Liang, Sonya Agarwal, A. Dimitrios Colevas, Alan Korman, Clint T. Allen, Ravindra Uppaluri, Albert C. Koong, Amato Giaccia, Quynh Thu Le

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