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Expression of the inhibitory B7 family molecule VISTA in human colorectal carcinoma tumors

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Abstract

Colorectal carcinoma (CRC) is one of the most common malignancies in the world. PD-1/PD-L1 inhibitors have benefited cancer patients with multiple tumor types. However, their efficacy for CRC is low and this treatment in melanoma patients results in adaptive resistance through upregulation of VISTA, another checkpoint inhibitory pathway. Thus, there is an urgent need to explore additional co-inhibitory molecular pathways such as VISTA for CRC treatment. In this study, C10orf54 (encoding VISTA) expression was analyzed by RNA-seq data from 367 CRC patients in human cancer datasets. Moreover, 28 clinical CRC specimens were used to assess VISTA protein expression. Human cancer datasets showed that CRC tumors expressed higher levels of C10orf54 than CD274 (encoding PD-L1). Moreover, C10orf54 mRNA expression was significantly correlated with genes responsible for tumor immune evasion. VISTA protein expression was high in tumors compared with para-tumors and normal tissues, which is similar to PD-L1 expression. However, in contrast to PD-L1, VISTA was mainly expressed by tumor-infiltrating lymphocytes. This study is the first investigation of VISTA expression in human resected CRC tumors, and the results justify the need for future studies on the role of VISTA in anti-CRC immunity in clinical samples.

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Abbreviations

COAD:

Colon adenocarcinoma

CRCL:

Colorectal carcinoma

dMMR:

Mismatch repair deficient

FDA:

Federal Drug Agency

HR:

Hazard ratio

MSI-H:

Microsatellite instability high

READ:

Rectum adenocarcinoma

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Acknowledgements

We greatly thank Dr. Gerard Zurawski at Baylor Institute for Immunology Research for reading this manuscript and providing constructive comments and suggestions. This work was supported by a grant from The National Natural Science Foundation of China (NSFC) (grant number 81502462).

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Author notes

  1. Shan Xie and Jia Huang contributed equally to this work.

Authors and Affiliations

  1. Institute for Immunology and School of Medicine, Tsinghua University, Medical Research Building, No.30 Haidian Shuangqing Road, Beijing, 100084, China

    Shan Xie, Qin Qiao, Wenjuan Zang, Shanjuan Hong, Chen Dong & Ling Ni

  2. Department of General Surgery, China-Japan Friendship Hospital, Beijing, 100029, China

    Jia Huang, Haidong Tan & Zhiying Yang

Authors
  1. Shan Xie
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  2. Jia Huang
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  3. Qin Qiao
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  7. Chen Dong
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  8. Zhiying Yang
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  9. Ling Ni
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Contributions

Shan Xie and Wenjuan Zang performed most of the experiments; Jia Huang, Qin Qiao, Shanjuan Hong and Haidong Tan performed some of the experiments or collected clinical specimens; Zhiying Yang supervised clinical specimens; Chen Dong and Ling Ni designed and supervised the study; Ling Ni wrote the manuscript.

Corresponding authors

Correspondence to Zhiying Yang or Ling Ni.

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Conflict of interest

The authors declare that there are no conflicts of interest to disclose.

Ethics statement

All procedures in this study were approved by the institutional review board at Tsinghua University and were performed in accordance with the institutional guidelines. All patients’ data were anonymized before study inclusion. Fresh specimens and matched blood of CRC patients without any therapies were obtained from the China-Japan Friendship Hospital in Beijing.

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Informed consent was obtained from all individual participants included in the study.

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Xie, S., Huang, J., Qiao, Q. et al. Expression of the inhibitory B7 family molecule VISTA in human colorectal carcinoma tumors. Cancer Immunol Immunother 67, 1685–1694 (2018). https://doi.org/10.1007/s00262-018-2227-8

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  • DOI: https://doi.org/10.1007/s00262-018-2227-8

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