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Persistence of tumor-infiltrating CD8 T cells is tumor-dependent but antigen-independent

Cellular & Molecular Immunology volume 8, pages 415–423 (2011)Cite this article

Abstract

How tumor-infiltrating lymphocytes (TILs) that are tumor-specific but functionally tolerant persist in the antigen-expressing tumor tissue is largely unknown. We have previously developed a modified TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model where prostate cancer cells express the T-cell epitope SIYRYYGL (SIY) recognized by CD8 T cells expressing the 2C T-cell receptor (TCR) (referred to as TRP-SIY mice). In TRP-SIY mice, activated 2C T cells rapidly become tolerant following infiltration into the prostate tumor. In this study, we show that tolerant 2C T cells persist in the prostate tumor of TRP-SIY mice by proliferating slowly in a tumor-dependent, but antigen-, interleukin (IL)-7- and IL-15-independent manner. We also show that disappearance of 2C T cells from the lymphoid organs of TRP-SIY mice are due to antigen-induced T-cell contraction rather than altered trafficking or generalized T-cell depletion in the mice. Finally, we show that clonal T cells unreactive to SIY are equally capable of persisting in the prostate tumor. These findings suggest that while functional tolerance of TILs is induced by antigen, persistence of tolerant TILs in the tumor tissue is mediated by a novel mechanism: slow proliferation independent of antigen and homeostatic cytokines. These results also allow CD8 T-cell survival in the tumor environment to be compared with T-cell survival in chronic infection.

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Acknowledgements

We thank Dr Paul Matsudaira for input and support for the project and Dr Herman N. Eisen and Dr Eileen M. Higham for carefully reviewing this manuscript, as well as Eileen M. Higham, Oezcan Talay, Ilya Leskov, Kristyn Ferber, Maria F. Fragoso, Carol McKinley and Camille Jusino for reagents and technical assistance. This work was supported by grants from the National Institutes of Health (F31-AI080286 to MO and CA100875 to JC), UNCF-Merck Graduate Research and NSF Graduate Research Fellowships (to MO) and Singapore-MIT Alliance and Koch Research Fund (to JC).

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Authors and Affiliations

  1. Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, USA

    Mobolaji O Olurinde

  2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Mobolaji O Olurinde, Ching-Hung Shen, Adam Drake, Ailin Bai & Jianzhu Chen

  3. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Mobolaji O Olurinde

  4. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

    Jianzhu Chen

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Correspondence to Jianzhu Chen.

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Olurinde, M., Shen, CH., Drake, A. et al. Persistence of tumor-infiltrating CD8 T cells is tumor-dependent but antigen-independent. Cell Mol Immunol 8, 415–423 (2011). https://doi.org/10.1038/cmi.2011.18

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