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Supplementary Table 1 from Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1–Resistant Tumors Leading to Tumor Eradication

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posted on 2023-04-03, 23:11 authored by Ainhoa Arina, Theodore Karrison, Eva Galka, Karin Schreiber, Ralph R. Weichselbaum, Hans Schreiber

Cytokine production by 2C CD8+ T cells from mice treated or not with allogeneic CD4+ T cells

Funding

NIH

The Berlin Institute of Health

The Einstein Foundation

The University of Chicago Cancer Center

Ludwig Foundation for Cancer Research at the University of Chicago

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ARTICLE ABSTRACT

Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T-cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD-1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist. Cancer Immunol Res; 5(2); 127–36. ©2017 AACR.

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