AUTHOR=Zhang Qun , Hu Jing , Zhang Yaping , Li Li , Wang Ting , Qian Xiaoping TITLE=Case report: A colorectal cancer patient with microsatellite instability-high and MSH2 germline mutation failed to respond to anti-PD-1 immunotherapy JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.953421 DOI=10.3389/fimmu.2022.953421 ISSN=1664-3224 ABSTRACT=

Lynch syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes. In colorectal cancer (CRC), germline mutations of DNA MMR genes commonly lead to microsatellite instability-high (MSI-H) subtype formation. Recent studies have demonstrated that CRC patients with MSI-H or mismatch repair-deficient (dMMR) status can benefit from anti-PD1 immunotherapy. However, almost 50% of CRC patients with MSI-H status do not respond to it. It is reported that heterogeneity of tumor and abnormal activation of cancer-related signaling pathways contribute to resistance to anti-PD1 therapy. To improve the clinical efficacy of such patients, the underlying mechanisms of resistance to anti-PD1 treatment must be explored. In this case, we describe an LS-associated CRC patient with MSI-H who suffered resistance to anti-PD1 therapy. Here, we attempted to elucidate the potential reasons, and thus appropriate strategies may be derived to overcome this clinical problem.