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

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

PROVIDER: PRJNA744780 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15069600_1.fastq.gz	Fastqsanger.gz
	SRR15069600_2.fastq.gz	Fastqsanger.gz
	SRR15069601_1.fastq.gz	Fastqsanger.gz
	SRR15069601_2.fastq.gz	Fastqsanger.gz
	SRR15069602_1.fastq.gz	Fastqsanger.gz

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

Project description:Neoadjuvant PD-1 blockade may be efficacious in patients 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 patients 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, 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 to Th17 T cells in pretreatment blood predicts innate resistance, low cytolytic T-cell signature in pretreatment tumor, and low T-cell receptor repertoire diversity in pretreatment blood. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for patients with resectable head-and-neck cancer.

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Project description:Response and recurrence correlates in patients treated with neoadjuvant anti-PD-1 therapy for resectable oral-cavity squamous cell carcinoma

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