What question did this study set out to answer?

To determine how neoantigen intratumor heterogeneity and clonal neoantigen burden influence antitumor immune responses and sensitivity to immune checkpoint blockade.

March 3, 2016ScienceOpen Access

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

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Authors

NMNicholas McGranahanLondon Cancer AFAndrew J.S. FurnessRoyal Marsden NHS Foundation Trust RRRachel RosenthalUniversity of Southern California

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Implication

Genomic analysis demonstrates that clonal neoantigen burden improves immunotherapy response and survival in lung cancer and melanoma, indicating the clinical value of targeting clonal mutations.

Key Points

To determine how neoantigen intratumor heterogeneity and clonal neoantigen burden influence antitumor immune responses and sensitivity to immune checkpoint blockade.
Conducted integrated genomic and bioinformatic analyses of intratumor heterogeneity and neoantigen burden across primary lung adenocarcinomas to evaluate survival associations.
Characterized CD8+ tumor-infiltrating lymphocyte reactivity and evaluated therapeutic responses to PD-1 and CTLA-4 inhibitors in cohorts of advanced non-small cell lung cancer and melanoma.
High clonal neoantigen burden correlated with extended overall survival in primary lung adenocarcinoma, and reactive CD8+ tumor-infiltrating lymphocytes in early-stage disease exhibited high PD-1 expression.
Enrichment for clonal neoantigens associated with enhanced response to PD-1 and CTLA-4 blockade in advanced disease, with reactive T cells persisting in patients achieving durable clinical benefit.
Chemotherapy-induced subclonal neoantigens elevated overall mutation load but were disproportionately enriched in tumors with poor responses to checkpoint inhibitors.

Cite This Study

McGranahan et al. (2016) studied this question.

synapsesocial.com/papers/69dd2d0d99c691022d99b45d https://doi.org/10.1126/science.aaf1490

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Implication

Genomic analysis demonstrates that clonal neoantigen burden improves immunotherapy response and survival in lung cancer and melanoma, indicating the clinical value of targeting clonal mutations.

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Discussion

Member takes

Implication

Key Points

Cite This Study

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade

Discussion

Member takes

Implication

Key Points

Cite This Study

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