AI Article Synopsis
- Tumors develop mutations as they grow, leading to neoantigens that can affect how well patients respond to immune therapies like checkpoint inhibitors.
- The study found a link between the number of clonal neoantigens in lung adenocarcinomas and patient survival, suggesting that the diversity of these neoantigens within tumors plays a crucial role in immune response.
- Patients with advanced lung cancer or melanoma showed better responses to immune therapies when their tumors had a higher presence of clonal neoantigens, highlighting the importance of understanding neoantigen diversity for improving cancer treatments.
Article Abstract
As tumors grow, they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on antitumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas. CD8(+)tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC and melanoma was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy-induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4984254 | PMC |
| http://dx.doi.org/10.1126/science.aaf1490 | DOI Listing |
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