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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Figure 1

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TA specificity and function of BM memory T cells from breast cancer pati...
TA specificity and function of BM memory T cells from breast cancer patients. (A) T cells were stained with tetramers containing HLA-A2 and the MUC1 peptide LLLLTVLTV or the irrelevant HIV peptide SLYNTVATL. Representative data are shown. Blue, low density of cells; yellow, high density of cells. (B and C) Frequencies of MUC1- or Her-2/neu–specific CD8+ T cells from BM and PB of patients (P) and healthy donors (HD). Maximal levels of tetramer-binding CD8+ T cells from healthy donors are depicted by dotted lines. Frequencies of HIV-specific CD8+ T cells from BM and PB of nine breast cancer patients are shown. Maximum levels of nonspecific bindings are depicted by solid lines. (D) Accumulative data for MUC1- and Her-2/neu–binding CD8+ T cells expressing memory markers (seven and six patients, respectively). *P < 0.0001, memory versus naive cells; *P < 0.0001, EM versus CM cells. (E) Frequencies of Her-2/neu–specific BM T cells from patients or healthy donors, measured by IFN-γ ELISPOT after stimulation by DCs pulsed with the Her-2/neu peptide KIFGSLAFL. (F) MUC1-specific cytotoxicity of BM T cells. Patient (filled squares and filled triangles) or donor (open circles) cells were stimulated for 5 days with DCs pulsed with the MUC1 peptide LLLLTVLTV. HLA-A2+ T2 target cells were loaded with LLLLTVLTV (filled squares, open circles) or SLYNTVATL (filled triangles) peptides. X axis represents effector/target (E/T) ratios.