{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T15:55:54Z","timestamp":1769010954549,"version":"3.49.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Deficient mismatch repair (dMMR) is an established biomarker for the response to the programmed cell death (PD)-1 inhibitors in metastatic colorectal cancer (mCRC). Although patients with dMMR mCRC could achieve a high incidence of disease control and favorable progression-free survival (PFS), reported response rates to PD-1 inhibitors are variable from 28% to 52%. We aimed to explore the additional predictive biomarkers associated with response to anti-PD-1 immunotherapy in patients with dMMR mCRC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter cohort study enrolled patients with dMMR mCRC receiving anti-PD-1 immunotherapy at the Sixth Affiliated Hospital of Sun Yat-sen University and Sun Yat-sen University Cancer Center between December 2016 and December 2019. The total information of 20 peripheral blood biomarkers, including T cells (frequency of CD4+ T cell, frequency of CD8+ T cell, and ratio of CD4+\/CD8+), carcinoembryonic antigen (CEA), inflammatory markers, and lipid metabolism markers, was collected. The association between response or survival and peripheral blood parameters was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the tested parameters, the ratio of CD4+\/CD8+ and frequency of CD4+ T cell were significantly associated with PFS (p = 0.023, p = 0.012) and overall survival (OS; p = 0.027, p = 0.019) in a univariate analysis. A lower level of CD4+\/CD8+ ratio or frequency of CD4+ T cell showed a significant association with better overall response rates (ORRs; p = 0.03, p = 0.01). The ratio of CD4+\/CD8+ and frequency of CD4+ T cell maintained significance in multivariate Cox model for PFS (HR = 9.23, p = 0.004; HR = 4.83, p = 0.02) and OS (HR = 15.22, p = 0.009; HR = 16.21, p = 0.025).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study indicated that the ratio of CD4+\/CD8+ and the frequency of CD4+ T cell might be crucial independent biomarkers within dMMR mCRC to better identify patients for anti-PD-1 immunotherapy. If validated in prospective clinical trials, the ratio of CD4+\/CD8+ and the frequency of CD4+ T cell might aid in guiding the treatment of PD-1 inhibitors among patients with dMMR mCRC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.809971","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T04:38:16Z","timestamp":1643863096000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Association of Peripheral Blood Biomarkers With Response to Anti-PD-1 Immunotherapy for Patients With Deficient Mismatch Repair Metastatic Colorectal Cancer: A Multicenter Cohort 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