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Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Although immune checkpoint inhibitors (ICIs) have achieved remarkable progress in the treatment of deficient mismatch repair (dMMR)\/high microsatellite instability (MSI-H) colorectal cancer (CRC), nearly 50% of dMMR\/MSI-H CRC patients exhibit primary resistance to immunotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case summary<\/jats:title><jats:p>An 84-year-old male patient was diagnosed with poorly differentiated adenocarcinoma of the right hemicolon (pT3N2M1c, stage IVc, dMMR). The patient underwent palliative surgery of the right hemicolon and subsequently received 3 cycles of bevacizumab in combination with capecitabine. Genetic testing revealed MSI-H\/TMB-H\/HLA heterozygosity. When the patient came to our center for treatment, we adjusted the treatment regimen to tislelizumab immunotherapy for 4 cycles. After immunotherapy, a CT review revealed disease progression. Moreover, the patient\u2019s physical strength deteriorated dramatically, with an Eastern Cooperative Oncology Group (ECOG) score of 3. The patient subsequently received best supportive care. The patient\u2019s overall survival (OS) was 9 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The continued success of immunotherapy in dMMR\/MSI-H CRC faces challenges related to immune resistance. Further studies are needed to uncover the mechanisms, targets, and biomarkers involved.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1636122","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T04:13:16Z","timestamp":1759810396000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Failed response to anti-PD-1 immunotherapy in a colon cancer patient with high microsatellite instability"],"prefix":"10.3389","volume":"15","author":[{"given":"Rong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ping","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Yan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Dai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Di","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jncc.2022.02.002","article-title":"Cancer incidence and mortality in China, 2016","volume":"2","author":"Zheng","year":"2022","journal-title":"J Natl Cancer Cent"},{"key":"B3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2478\/v10019-011-0005-8","article-title":"Microsatellite instability in colorectal cancer","volume":"45","author":"Horvat","year":"2011","journal-title":"Radiol Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1200\/PO.17.00073","article-title":"Landscape of microsatellite instability across 39 cancer types","volume":"2017","author":"Bonneville","year":"2017","journal-title":"JCO Precis Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s11725-015-0588-4","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"9","author":"Aparicio","year":"2015","journal-title":"Colon Rectum"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01015","article-title":"First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high\/mismatch repair-deficient metastatic colorectal cancer: the phase II checkMate 142 study","volume":"40","author":"Lenz","year":"2022","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.519","article-title":"Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study","volume":"33","author":"Maio","year":"2022","journal-title":"Ann Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699","article-title":"Diaz LA jr; KEYNOTE-177 investigators. 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