Abstract
Objective
Oropharyngeal squamous cell carcinoma (OPSCC) recurrence is almost universally fatal. Development of effective therapeutic options requires an improved understanding of recurrent OPSCC biology.
Methods
We analyzed paired primary-recurrent OPSCC from Veterans treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who received curative intent radiation-based treatment (with or without chemotherapy). Patient tumors were analyzed using standard immunohistochemistry and automated imaging of infiltrating lymphocytes and multinucleated tumor cells coupled to machine learning algorithms.
Results
Primary and recurrent tumors demonstrated high concordance via p16 and p53 immunohistochemistry, with comparable levels of multinucleation. In contrast, recurrent tumors demonstrated significantly higher levels of CD8+ tumor infiltrating lymphocytes (p<0.05) and higher levels of PD-L1 expression (p<0.05).
Conclusion
Exposure to chemo-radiation and recurrence following treatment preserves critical features of intrinsic tumor biology and the tumor immune microenvironment suggesting that novel treatment regimens may be as effective in the salvage setting as in the definitive intent setting.
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Funding
This work was supported by a Career Development Award to VCS from the Veterans Administration Clinical Science Research and Development division (1IK2CX001953) and through the Dan L Duncan Comprehensive Cancer Center (P30-CA125123) and Human Tissue Acquisition & Pathology Core Baylor College of Medicine. Dr Madabhushi’s work is supported from grants supported by the National Cancer Institute under award numbers 1U24CA199374-01, R01CA249992-01A1, R01CA202752-01A1, R01CA208236-01A1, R01CA216579-01A1, R01CA220581-01A1, R01CA257612-01A1, 1U01CA239055-01, 1U01CA248226-01, 1U54CA254566-01, National Heart, Lung and Blood Institute 1R01HL15127701A1, R01HL15807101A1, National Institute of Biomedical Imaging and Bioengineering 1R43EB028736-01, National Center for Research Resources under award number 1 C06 RR12463-01; VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program (W81XWH-19-1-0668), the Prostate Cancer Research Program (W81XWH-15-1-0558, W81XWH-20-1-0851), the Lung Cancer Research Program (W81XWH-18-1-0440, W81XWH-20-1-0595), the Peer Reviewed Cancer Research Program (W81XWH-18-1-0404, W81XWH-21-1-0345), the Kidney Precision Medicine Project (KPMP) Glue Grant, the Ohio Third Frontier Technology Validation Fund, the Mayo Clinic Breast Cancer SPORE grant P50 CA116201 from the National Institutes of Health, the Clinical and Translational Science Collaborative of Cleveland (UL1TR0002548) from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research, The Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering at Case Western Reserve University, sponsored research agreements from Bristol Myers-Squibb, Boehringer-Ingelheim, and AstraZeneca.
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PC, GC, CK, LAN, TJ, TL collected and analyzed the data. JSL, AM, MJF, VCS supervised data analysis and provided quality assurance for all data collection and analysis. PC, GC, CK, JSL, AM, MJ, VCS drafted the manuscript. All authors reviewed and participated in the revision process for the manuscript. PC and VCS prepared the figures.
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There are no conflicts of interest directly related to this work. Dr. Sandulache is a consultant for Femtovox Inc. Dr. Madabhushi is an equity holder in Picture Health, Elucid Bioimaging, and Inspirata Inc. Currently he serves on the advisory board of Picture Health, Aiforia Inc, and SimBioSys. He also currently consults for Roche, Biohme, and Castle Biosciences. He also has sponsored research agreements with AstraZeneca, Boehringer-Ingelheim, Eli-Lilly and Bristol Myers-Squibb. His technology has been licensed to Picture Health and Elucid Bioimaging. He is also involved in 3 different R01 grants with Inspirata Inc.
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Castro, P., Corredor, G., Koyuncu, C. et al. Recurrent Oropharyngeal Squamous Cell Carcinomas Maintain Anti-tumor Immunity and Multinucleation Levels Following Completion of Radiation. Head and Neck Pathol 17, 952–960 (2023). https://doi.org/10.1007/s12105-023-01597-z
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DOI: https://doi.org/10.1007/s12105-023-01597-z