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Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8+ T cells in gastric cancer

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Abstract

With dichotomous etiology and pathogenesis, intestinal type and diffuse type gastric cancers vary in their clinical and molecular features to the point of representing distinct entities. However, the differences of tumor-infiltrating immune cells within the two types of gastric cancer have not been well researched. This study was aimed to evaluate the functional impact of Lauren classification on immune contexture in gastric cancer patients. Tumor tissues of gastric cancer patients from Zhongshan Hospital and gastric cancer data from The Cancer Genome Atlas (TCGA) cohort were analyzed. By immunohistochemistry and flow cytometry, we found that intratumoral CD8+ T cells were more abundant but less functional in diffuse type as compared with those in intestinal type tumor tissues. Survival analysis indicated that CD8+ T cells yielded favorable prognosis only in intestinal type patients other than diffuse type cancer patients. Moreover, such diffuse type-associated CD8+ T cell dysfunction was featured by elevated expression of immunosuppressive factors including interleukin-10 (IL-10), transforming growth factor-β1 (TGF-β1) and indoleamine 2,3-dioxygenase 1 (IDO1). In summary, we found that the density, prognostic significance and functional status of intratumoral CD8+ T cells varied with Lauren subtypes in gastric cancer. These results further indicated Lauren classification might be a potential therapeutic marker, and should be considered in therapeutic decisions, especially immunotherapeutic eligibility.

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Acknowledgments

Not applicable.

Funding

This study was funded by Grants from National Natural Science Foundation of China (81671628, 81672324, 31770851, 81871306, 81871926, 81871930, 81902402, 81902901, 81972219), Shanghai Municipal Natural Science Foundation (18ZR1432900) and Shanghai Sailing Program (17YF1402200, 18YF1404600, 19YF1407500). All these study sponsors have no roles in the study design, in the collection, analysis and interpretation of data.

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Author notes

  1. Ruochen Li, Heng Zhang, Yifan Cao, and Xin Liu have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Ruochen Li, Heng Zhang, Yifan Cao, Kuan Yu, Chao Lin, Hao Liu, Hongyong He, He Li, Zhenbin Shen, Jing Qin & Yihong Sun

  2. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Xin Liu & Jiejie Xu

  3. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China

    Yifan Chen, Yangyang Qi & Weijuan Zhang

  4. Department of Gastric Surgery, Shanghai Cancer Center, Fudan University, Shanghai, China

    Jieti Wang

  5. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

    Lingli Chen

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  1. Ruochen Li
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Contributions

In this study, RCL, HZ, YFC and XL involved in acquisition of data, analysis and interpretation of data and drafting of the manuscript; RCL took part in the statistical analysis; YFC, YYQ, HL, JTW, KY, LLC, CL, HYH, HL, ZBS, JQ and WJZ took part in technical and material support; YHS and JJX participated in study concept and design, analysis and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.

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Correspondence to Yihong Sun or Jiejie Xu.

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Li, R., Zhang, H., Cao, Y. et al. Lauren classification identifies distinct prognostic value and functional status of intratumoral CD8+ T cells in gastric cancer. Cancer Immunol Immunother 69, 1327–1336 (2020). https://doi.org/10.1007/s00262-020-02550-7

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