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Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway

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Abstract

Although the incidence rate and mortality of gastric/gastroesophageal cancer (G/GEJC) are declining globally, G/GEJC remains a health issue in East Asia. When diagnosed as advanced stage, treatment after serial lines of chemotherapy is limited, with a median overall survival of less than 1 year. Immunotherapy, including immune checkpoint inhibitors (ICIs) and cellular immunotherapy, has changed the prospects of cancer therapy by reversing immune suppression in the tumor microenvironment. As part of this review, we enumerated the clinical uses of ICIs related to the immunosuppressive signaling axis PD-1/PD-L1 and CTLA-4/B7. ICIs were initially approved as a secondary treatment option for patients with severe pretreating advanced gastric and gastroesophageal cancer (AG/GEJC). Till now, it has become the mainstream therapy in combination with chemotherapy and targeted therapy for patients identified by biomarkers. Numerous evidence showed microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1) expression, tumor mutation burden (TMB) and Epstein–Barr virus (EBV) status might be indicative to the use of ICIs. In addition, we discussed the current limitations and prospects of ICIs in AG/GGEJC, as well as the first clinical application of novel CAR-T cell therapies.

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  1. Runzi Cheng and Baizhi Li have contributed equally to this work and share first authorship.

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  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China

    Runzi Cheng, Huaiming Wang & Yongming Zeng

  2. Shantou University Medical College, Shantou, People’s Republic of China

    Runzi Cheng & Baizhi Li

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Conceptualization, all authors; writing—original draft preparation, RC; writing—review and editing, RC, BL, HW, YZ. All authors have read and agreed to the published version of the manuscript.

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Cheng, R., Li, B., Wang, H. et al. Immune checkpoint inhibitors and cellular immunotherapy for advanced gastric, gastroesophageal cancer: a long pathway. Clin Transl Oncol 25, 3122–3138 (2023). https://doi.org/10.1007/s12094-023-03181-x

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