Association of Peripheral Blood Biomarkers With Response to Anti-PD-1 Immunotherapy for Patients With Deficient Mismatch Repair Metastatic Colorectal Cancer: A Multicenter Cohort Study.

Abstract

Purpose:

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.

Methods:

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.

Results:

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).

Conclusion:

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.

• Authors: Yi-Kan Cheng, Dong-Wen Chen, Ping Chen, Xiaosheng He, Pei-Si Li, Zhen-Sen Lin, Shao-Xia Chen, Shu-Biao Ye, Ping Lan
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 809971 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35185898 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Cheng, Chen, Chen, He, Li, Lin, Chen, Ye and Lan.

Chemical References

• Biomarkers, Tumor
• Immune Checkpoint Inhibitors

Topics

• Adult
• Aged
• Biomarkers, Tumor (genetics)
• CD4-Positive T-Lymphocytes (metabolism)
• CD8-Positive T-Lymphocytes (metabolism)
• Cohort Studies
• Colorectal Neoplasms (drug therapy, genetics, immunology)
• DNA Mismatch Repair
• Female
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Male
• Middle Aged
• Progression-Free Survival
• Young Adult