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TIGIT promotes CD8+T cells exhaustion and predicts poor prognosis of colorectal cancer

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Abstract

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8+T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT+CD8+T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT+CD8+T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT+CD8+T cells. TGF-β1 could promote the expression of TIGIT and inhibit CD8+T cell function in vitro. Moreover, the accumulation of TIGIT+T cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.

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Data availability

The data used in this study are available from the corresponding author on reasonable request.

Abbreviations

CRC:

Colorectal cancer

IFN-γ:

Interferon γ

IL-2:

Interleukin-2

LAG-3:

Lymphocyte-activation gene 3

NK cells:

Natural killer cells

PBMC:

Peripheral blood mononuclear cell

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed cell death ligand 1

TGF-β:

Transforming growth factor-β

TIGIT:

T cell immunoreceptor with Ig and ITIM domains

TILs:

Tumor-infiltrating lymphocytes

TIM-3:

T cell immunoglobulin and mucin domain-3

TNF-α:

Tumor necrosis factor-α

Tregs:

Regulatory T cells

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Acknowledgements

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Funding

This work was supported in part by grants from the Science and Technology Planning Project of Guangdong Province (2017B020227009 to Bo Wei).

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Author notes

  1. Rongpu Liang and Xudong Zhu Equally contributed authors.

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510630, People’s Republic of China

    Rongpu Liang, Xudong Zhu, Dongbing Ding, Zongheng Zheng, Tufeng Chen, Yong Huang, Jianpei Liu, Xiaofeng Yang, Jun Shao, Hongbo Wei & Bo Wei

  2. Central Laboratory, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, Guangdong, People’s Republic of China

    Tianyun Lan

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  1. Rongpu Liang
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Contributions

R.L. and B.W. contributed to conceived and designed the experiments; R.L., X.Z., and B.W. were involved in analyzed the data; R.L. and X.Z. contributed to performed the experiments and writing — original draft; B.W. was involved in writing —review and editing and funding acquisition; T.L., D.D., X.Y., and J.S contributed to assisted during the experiment; H.W. was involved in given guidance on research ideas during the research process; and Z.Z., T.C., Y.H., and J.L. contributed to provided clinical samples and information.

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Correspondence to Hongbo Wei or Bo Wei.

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This study was executed under ethical approvals from The Third Affiliated Hospital of Sun Yat-Sen University.

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Liang, R., Zhu, X., Lan, T. et al. TIGIT promotes CD8+T cells exhaustion and predicts poor prognosis of colorectal cancer. Cancer Immunol Immunother 70, 2781–2793 (2021). https://doi.org/10.1007/s00262-021-02886-8

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