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CASE REPORT article

Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1484802
This article is part of the Research Topic Exploring DNA Repair Defects and Metabolic Vulnerability to Enhance Immunotherapy response View all articles

Negative response to immunotherapy in dMMR or MSI-H gastric cancer with APC and PTEN mutations: A case report

Provisionally accepted
Jiang Liu Jiang Liu 1,2*Xiumei Zhang Xiumei Zhang 1,2*Qun Ren Qun Ren 1,2*Chuanjun Song Chuanjun Song 1,2Jianhe Yu Jianhe Yu 1,2*Yin Cai Yin Cai 1,2*Dadong Chen Dadong Chen 1,2*
  • 1 Affiliated Hospital of Yangzhou University, Yangzhou, China
  • 2 Xinghua People's Hospital, xinghua, China

The final, formatted version of the article will be published soon.

    Background: Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) represents a distinct molecular phenotype observed in malignant tumors. These tumors typically exhibit high levels of programmed cell death 1 ligand 1 (PD-L1) expression and high tumor mutational burden (TMB), resulting in an enhanced response to immune checkpoint inhibitors (ICI) therapy. The emergence of ICI has transformed the therapeutic strategy of gastric cancer (GC). Immune checkpoint blockade significantly improves the survival of gastric cancer patients, especially those with MSI-H or dMMR. However, it's worth noting that not all patients with MSI-H respond favorably to this treatment. It has been reported that factors such as tumor heterogeneity, alterations in the tumor microenvironment, and aberrant activation of tumor-related signaling pathways have been linked with resistance to ICI therapy.Here, we describe a case of dMMR and MSI-H GC with adenomatous polyposis coli (APC) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) mutations that failed to respond to anti-PD-1 combined with anti-HER2 (human epidermal growth factor receptor-2) therapy and chemotherapy.We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients.Conclusions: Mutations of key genes within tumor-related signaling pathways and the infiltration of CD8 + T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.

    Keywords: Microsatellite instability high, Mismatch repair-deficient, gastric cancer, Immunotherapy, case report

    Received: 22 Aug 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Liu, Zhang, Ren, Song, Yu, Cai and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jiang Liu, Affiliated Hospital of Yangzhou University, Yangzhou, China
    Xiumei Zhang, Xinghua People's Hospital, xinghua, China
    Qun Ren, Affiliated Hospital of Yangzhou University, Yangzhou, China
    Jianhe Yu, Affiliated Hospital of Yangzhou University, Yangzhou, China
    Yin Cai, Affiliated Hospital of Yangzhou University, Yangzhou, China
    Dadong Chen, Affiliated Hospital of Yangzhou University, Yangzhou, China

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