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Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer

Cellular & Molecular Immunology volume 7, pages 389–395 (2010)Cite this article

Abstract

T-cell tolerance is an important mechanism for tumor escape, but the molecular pathways involved in T-cell tolerance remain poorly understood. It remains unknown whether the inhibitory immunoreceptor programmed death-1 (PD-1) plays a role in conditions of human non-small cell lung cancer (NSCLC). In this study, we detected PD-1 expression on CD8+ T cells from healthy control peripheral blood mononuclear cells (PBMCs) and the PBMCs of NSCLC patients as well as NSCLC tissues. Results showed that tumor-infiltrating CD8+ T cells had increased PD-1 expression and impaired immune function, including reducing cytokine production capability and impairing capacity to proliferate. Blockade of the PD-1/PD-L1 pathway by the PD-L1-specific antibody partially restored cytokine production and cell proliferation. These data provide direct evidence that the PD-1/PD-L1 pathway is involved in CD8+ T-cell dysfunction in NSCLC patients. Moreover, blocking this pathway provides a potential therapy target in lung cancer.

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Acknowledgements

This work was supported by Grant 2006AA02A247 from the National High Biotechnology Development Program of China.

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Authors and Affiliations

  1. Department of Laboratory Diagnosis, Changhai Hospital, Second Military Medical University, Shanghai, China

    Yan Zhang, Yanghua Qin & Qian Shen

  2. Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China

    Shengdong Huang & Dejun Gong

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  1. Yan Zhang
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Correspondence to Qian Shen.

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Zhang, Y., Huang, S., Gong, D. et al. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 7, 389–395 (2010). https://doi.org/10.1038/cmi.2010.28

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