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

Sixue Liu; Hannah M. Knochelmann; Shirley H. Lomeli; Aayoung Hong; Mary Richardson; Zhentao Yang; Raymond J. Lim; Yan Wang; Camelia Dumitras; Kostyantyn Krysan; Cynthia Timmers; Martin J. Romeo; Carsten Krieg; Elizabeth C. O’Quinn; Joshua D. Horton; Steve M. Dubinett; Chrystal M. Paulos; David M. Neskey; Roger S. Lo

Cell Reports Medicine (Oct 2021)

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

Sixue Liu,
Hannah M. Knochelmann,
Shirley H. Lomeli,
Aayoung Hong,
Mary Richardson,
Zhentao Yang,
Raymond J. Lim,
Yan Wang,
Camelia Dumitras,
Kostyantyn Krysan,
Cynthia Timmers,
Martin J. Romeo,
Carsten Krieg,
Elizabeth C. O’Quinn,
Joshua D. Horton,
Steve M. Dubinett,
Chrystal M. Paulos,
David M. Neskey,
Roger S. Lo

Affiliations

Sixue Liu: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Hannah M. Knochelmann: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA
Shirley H. Lomeli: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Aayoung Hong: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Mary Richardson: Department of Pathology, Medical University of South Carolina, Charleston, SC 29425, USA
Zhentao Yang: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Raymond J. Lim: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Yan Wang: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Camelia Dumitras: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Kostyantyn Krysan: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Cynthia Timmers: Incyte Pharmaceuticals, Wilmington, DE 19803, USA
Martin J. Romeo: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA
Carsten Krieg: Department of Immunology and Microbiology, Medical University of South Carolina, Charleston, SC 29425, USA
Elizabeth C. O’Quinn: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA
Joshua D. Horton: Department of Otolaryngology – Head and Neck Surgery, Medical University of South Carolina, Charleston, SC 29425, USA
Steve M. Dubinett: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Chrystal M. Paulos: Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
David M. Neskey: Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Otolaryngology – Head and Neck Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA
Roger S. Lo: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Corresponding author

Journal volume & issue: Vol. 2, no. 10
p. 100411

Abstract

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Summary: 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.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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