Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors
Philipp Beckhove, … , Volker Schirrmacher, Viktor Umansky
Philipp Beckhove, … , Volker Schirrmacher, Viktor Umansky
Published July 1, 2004
Citation Information: J Clin Invest. 2004;114(1):67-76. https://doi.org/10.1172/JCI20278.
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Article Oncology

Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors

Abstract

Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.

Authors

Philipp Beckhove, Markus Feuerer, Mathias Dolenc, Florian Schuetz, Carmen Choi, Nora Sommerfeldt, Jochen Schwendemann, Katrin Ehlert, Peter Altevogt, Gunther Bastert, Volker Schirrmacher, Viktor Umansky

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Characterization of tumor-infiltrating cells after ADI. Breast cancer or...
Characterization of tumor-infiltrating cells after ADI. Breast cancer or normal skin specimens from three patients were xenotransplanted into five mice. (A) Staining with mAb against CD3 21 days after transfer of autologous memory or naive T cells into tumor-bearing mice. (B) Phenotype of tumor-infiltrating memory T cells 21 days after their transfer into tumor-bearing mice. Tumor tissue was stained with mAb’s against CD4, CD8, CD45R0, and CD45RA. Slides from A and B were counterstained with hemalaun. (C) Colocalization of transferred DCs (CD11c, dark blue; arrows) and T cells (red; arrowheads) within tumor tissue 21 days after adoptive transfer. Original magnifications, ×250 (A and B) and ×400 (C). (D) Numbers of CD3+ T cells and CD11c+ DCs in tumor or skin transplants determined by immunohistochemistry at day 9 and day 21 after ADI (black bars) and from untreated mice (white bars). Tumor and skin transplants from untreated mice (white bars) were used as a control. Means ± SD from three independent experiments (specimens from three patients transplanted into five mice) are depicted. Three sections per transplant and mouse were analyzed. *P < 0.05, significant differences compared with corresponding untreated controls.