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Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates with CD38 and Tim-3 expression

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Abstract

The efficacy of immunotherapy in cancer patients is influenced by differences in their immune status. An evaluation of immunocompetence before therapy may help to predict therapeutic success and guide the selection of appropriate regimens. We assessed the preexisting cellular immunity against prostate-specific antigen (PSA) in untreated prostate cancer patients and healthy controls through measurement of the phenotype and function of CD8+ T cells. Our data show that the majority of healthy men possess functional PSA-specific CD8+ T cells in contrast to cancer patients, where <50 % showed a CD8+ T cell response. PSA146–154-specific CD8+ T cells of these patients had a higher expression of the activation marker CD38 and the exhaustion marker Tim-3, indicating that PSA-specific cells are exhausted. The heterogeneity of the CD8+ T cell response against PSA in prostate cancer patients may influence their response to therapy and is a factor to be taken into account while designing and selecting treatment regimens.

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Abbreviations

CTLA-4:

Cytotoxic T lymphocyte antigen 4

HD:

Healthy donors

HLA:

Human leukocyte antigen

MHC:

Major histocompatibility complex

PBMCs:

Peripheral blood mononuclear cells

PCa:

Prostate cancer

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed death-ligand 1

PSA:

Prostate-specific antigen

Tim-3:

T cell immunoglobulin and mucin domain 3

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Acknowledgments

The authors thank Beate Möwes and the BCRT Flow Cytometry Lab for expert technical help. This work was supported by the German Research Foundation (DFG) Sonderforschungsbereich Transregio 36 (SFB TR36) and Th 806/5-1, and a flexible funds grant from the Berlin-Brandenburg Center for Regenerative Therapies/Federal Ministry of Education and Research (BCRT/BMBF).

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    Authors and Affiliations

    1. Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany

      Alberto Sada Japp, M. Alper Kursunel, Sarah Meier, Julia N. Mälzer, Andreas Thiel & Marco Frentsch

    2. State Key Laboratory of Agro-Biotechnology China, Agricultural University, Beijing, 100193, China

      Xiangdong Li

    3. Department of Physiology, Faculty of Medicine, Institute of Biomedicine, University of Turku, 20520, Turku, Finland

      Nafis A. Rahman

    4. Department of Urology, Charité University Medicine, 10117, Berlin, Germany

      Waltraut Jekabsons, Hans Krause, Ahmed Magheli & Christian Klopf

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    Alberto Sada Japp and M. Alper Kursunel as well as Andreas Thiel and Marco Frentsch have contributed equally to this work.

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    Japp, A.S., Kursunel, M.A., Meier, S. et al. Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates with CD38 and Tim-3 expression. Cancer Immunol Immunother 64, 1487–1494 (2015). https://doi.org/10.1007/s00262-015-1752-y

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