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TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types.


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.

SUBMITTER: Cao JZ 

PROVIDER: S-EPMC9004558 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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TP53/BRAF mutation as an aid in predicting response to immune-checkpoint inhibitor across multiple cancer types.

Cao Jia-Zheng JZ   Yao Gao-Sheng GS   Liu Fei F   Tang Yi-Ming YM   Li Peng-Ju PJ   Feng Zi-Hao ZH   Luo Jun-Hang JH   Wei Jin-Huan JH  

Aging 20220327 6


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  ...[more]

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