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Publication

Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma.

Cell reports. Medicine | 2021

Neoadjuvant PD-1 blockade may be efficacious in some individuals with high-risk, resectable oral cavity head and neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 individuals displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, or JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T cell clones. A high ratio of regulatory T to T helper 17 cells in pretreatment blood predicts low T cell receptor repertoire diversity in pretreatment blood, a low cytolytic T cell signature in pretreatment tumors, and innate resistance. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for individuals with resectable head and neck cancer.

Pubmed ID: 34755131 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: R21 CA215910
Agency: NCI NIH HHS, United States
Id: R21 CA255837
Agency: NCI NIH HHS, United States
Id: R01 CA208514
Agency: NCI NIH HHS, United States
Id: R01 CA175061
Agency: NCI NIH HHS, United States
Id: R01 CA176111
Agency: NCI NIH HHS, United States
Id: P30 CA016042
Agency: NCI NIH HHS, United States
Id: T32 CA009120
Agency: NCI NIH HHS, United States
Id: P01 CA244118
Agency: NCATS NIH HHS, United States
Id: UL1 TR001450
Agency: NIDCR NIH HHS, United States
Id: R21 DE029592
Agency: NCI NIH HHS, United States
Id: P30 CA138313
Agency: NCI NIH HHS, United States
Id: P01 CA168585
Agency: NIDCR NIH HHS, United States
Id: K08 DE026542

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