Research Paper Volume 14, Issue 6 pp 2868—2879
TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types
- 1 Department of Urology, Jiangmen Central Hospital, Jiangmen, Guangdong, China
- 2 Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- 3 Department of Urology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Received: September 17, 2021 Accepted: February 11, 2022 Published: March 27, 2022
https://doi.org/10.18632/aging.203980How to Cite
Copyright: © 2022 Cao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Immunotherapy with checkpoint inhibitors, such as PD-1/PD-L1 blockage, is becoming standard of practice for an increasing number of cancer types. However, the response rate is only 10%-40%. Thus, identifying biomarkers that could accurately predict the ICI-therapy response is critically important. We downloaded somatic mutation data for 46,697 patients and tumor-infiltrating immune cells levels data for 11070 patients, then combined TP53 and BRAF mutation status into a biomarker model and found that the predict ability of TP53/BRAF mutation model is more powerful than some past models. Commonly, patients with high-TMB status have better response to ICI therapy than patients with low-TMB status. However, the genotype of TP53MUTBRAFWT in high-TMB status cohort have poorer response to ICI therapy than the genotype of BRAFMUTTP53WT in low-TMB status (Median, 18 months vs 47 month). Thus, TP53/BRAF mutation model can add predictive value to TMB in identifying patients who benefited from ICI treatment, which can enable more informed treatment decisions.