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The mutational pattern of homologous recombination-related (HRR) genes in Chinese colon cancer and its relevance to immunotherapy responses
Background: Microsatellite-stable (MSS) colon adenocarcinoma (COAD) patients are not sensitive to immune checkpoint inhibitors. Here, we focused on analyzing the relationship between homologous recombination repair (HRR)-related gene mutations and clinical immunotherapy responses in MSS COAD. Method...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880324/ https://www.ncbi.nlm.nih.gov/pubmed/33318301 http://dx.doi.org/10.18632/aging.202267 |
Sumario: | Background: Microsatellite-stable (MSS) colon adenocarcinoma (COAD) patients are not sensitive to immune checkpoint inhibitors. Here, we focused on analyzing the relationship between homologous recombination repair (HRR)-related gene mutations and clinical immunotherapy responses in MSS COAD. Methods: The mutational landscape was profiled in a cohort of 406 Chinese COAD patients via next-generation sequencing (NGS). Correlations between HRR gene mutations and tumor immunity or clinical outcomes in two COAD genomic datasets were analyzed via bioinformatics. Results: In the Chinese cohort, seventy (17%) patients exhibited genomic alterations in HRR genes; ATM (9%), BRCA2 (4%), ATR (3%), RAD50 (3%) and BRIP1 (3%) were the most frequently mutated. In the MSK-IMPACT COAD cohort (immune checkpoint inhibitor-treated), HRR-mut patients (n=34) survived longer than HRR-wt patients (n=50) (log-rank P < 0.01). Based on the TCGA MSS COAD cohort, HRR gene mutations increased immune activities, such as infiltration of cytotoxic cells (P < 0.05) and exhausted CD8+ T cells (P < 0.01), and increased the IFN-γ scores (P < 0.05). The results differed in MSI-H COAD patients (all P > 0.05). Conclusion: HRR gene mutations significantly increased immune activities in MSS COAD patients, implying the feasibility of the HRR-mut status as an immunotherapy response predictor in MSS COAD. |
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