Neoantigen immunogenicity landscapes and evolution of tumor ecosystems during immunotherapy with nivolumab Journal Article
| Authors: | Alban, T. J.; Riaz, N.; Parthasarathy, P.; Makarov, V.; Kendall, S.; Yoo, S. K.; Shah, R.; Weinhold, N.; Srivastava, R.; Ma, X.; Krishna, C.; Mok, J. Y.; van Esch, W. J. E.; Garon, E.; Akerley, W.; Creelan, B.; Aanur, N.; Chowell, D.; Geese, W. J.; Rizvi, N. A.; Chan, T. A. |
| Article Title: | Neoantigen immunogenicity landscapes and evolution of tumor ecosystems during immunotherapy with nivolumab |
| Abstract: | Neoantigen immunoediting drives immune checkpoint blockade efficacy, yet the molecular features of neoantigens and how neoantigen immunogenicity shapes treatment response remain poorly understood. To address these questions, 80 patients with non-small cell lung cancer were enrolled in the biomarker cohort of CheckMate 153 (CA209-153), which collected radiographic guided biopsy samples before treatment and during treatment with nivolumab. Early loss of mutations and neoantigens during therapy are both associated with clinical benefit. We examined 1,453 candidate neoantigens, including many of which that had reduced cancer cell fraction after treatment with nivolumab, and identified 196 neopeptides that were recognized by T cells. Mapping these neoantigens to clonal dynamics, evolutionary trajectories and clinical response revealed a strong selection against immunogenic neoantigen-harboring clones. We identified position-specific amino acid and physiochemical features related to immunogenicity and developed an immunogenicity score. Nivolumab-induced microenvironmental evolution in non-small cell lung cancer shared some similarities with melanoma, yet critical differences were apparent. This study provides unprecedented molecular portraits of neoantigen landscapes underlying nivolumab’s mechanism of action. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. |
| Keywords: | controlled study; treatment response; middle aged; genetics; mutation; t lymphocyte; t-lymphocytes; carcinoma, non-small-cell lung; lung neoplasms; drug effect; pathology; tumor antigen; lung tumor; antigen presentation; immunology; immunotherapy; antigens, neoplasm; immunogenicity; cancer cell; cell fractionation; drug therapy; non small cell lung cancer; tumor microenvironment; immunoediting; procedures; nivolumab; humans; human; male; female; article; whole exome sequencing; immunological antineoplastic agent; antineoplastic agents, immunological |
| Journal Title: | Nature Medicine |
| Volume: | 30 |
| Issue: | 11 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-11-01 |
| Start Page: | 3209 |
| End Page: | 3222 |
| Language: | English |
| DOI: | 10.1038/s41591-024-03240-y |
| PUBMED: | 39349627 |
| PROVIDER: | scopus |
| PMCID: | PMC12066197 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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