Compartmentalized spatial profiling of the tumor microenvironment in head and neck squamous cell carcinoma identifies immune checkpoint molecules and tumor necrosis factor receptor superfamily members as biomarkers of response to immunotherapy.

Autor:	Sadeghirad H; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Liu N; Department of Bioinformatics Devision, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia.; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Monkman J; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Ma N; Akoya Biosciences, Menlo Park, California, CA, United States., Cheikh BB; Akoya Biosciences, Menlo Park, California, CA, United States., Jhaveri N; Akoya Biosciences, Menlo Park, California, CA, United States., Tan CW; Department of Bioinformatics Devision, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia.; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia., Warkiani ME; School of Biomedical Engineering, University of Technology, Sydney, NSW, Australia., Adams MN; School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia., Nguyen Q; Institute of Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia., Ladwa R; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.; The Princess Alexandra Hospital, Brisbane, QLD, Australia., Braubach O; Akoya Biosciences, Menlo Park, California, CA, United States., O'Byrne K; School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, Australia.; The Princess Alexandra Hospital, Brisbane, QLD, Australia., Davis M; Department of Bioinformatics Devision, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia.; Department of Medical Biology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.; South Australian immunoGENomics Cancer Institute, The University of Adelaide, Adelaide, SA, Australia., Hughes BGM; The Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia., Kulasinghe A; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Apr 03; Vol. 14, pp. 1135489. Date of Electronic Publication: 2023 Apr 03 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1135489
Abstrakt:	Mucosal head and neck squamous cell carcinoma (HNSCC) are the seventh most common cancer, with approximately 50% of patients living beyond 5 years. Immune checkpoint inhibitors (ICIs) have shown promising results in patients with recurrent or metastatic (R/M) disease, however, only a subset of patients benefit from immunotherapy. Studies have implicated the tumor microenvironment (TME) of HNSCC as a major factor in therapy response, highlighting the need to better understand the TME, particularly by spatially resolved means to determine cellular and molecular components. Here, we employed targeted spatial profiling of proteins on a cohort of pre-treatment tissues from patients with R/M disease to identify novel biomarkers of response within the tumor and stromal margins. By grouping patient outcome categories into response or non-response, based on Response Evaluation Criteria in Solid Tumors (RECIST) we show that immune checkpoint molecules, including PD-L1, B7-H3, and VISTA, were differentially expressed. Patient responders possessed significantly higher tumor expression of PD-L1 and B7-H3, but lower expression of VISTA. Analysis of response subgroups indicated that tumor necrosis factor receptor (TNFR) superfamily members including OX40L, CD27, 4-1BB, CD40, and CD95/Fas, were associated with immunotherapy outcome. CD40 expression was higher in patient-responders than non responders, while CD95/Fas expression was lower in patients with partial response (PR) relative to those with stable disease (SD) and progressive disease (PD). Furthermore, we found that high 4-1BB expression in the tumor compartment, but not in the stroma, was associated with better overall survival (OS) (HR= 0.28, p-adjusted= 0.040). Moreover, high CD40 expression in tumor regions (HR= 0.27, p-adjusted= 0.035), and high CD27 expression in the stroma (HR= 0.2, p-adjusted=0.032) were associated with better survival outcomes. Taken together, this study supports the role of immune checkpoint molecules and implicates the TNFR superfamily as key players in immunotherapy response in our cohort of HNSCC. Validation of these findings in a prospective study is required to determine the robustness of these tissue signatures. Competing Interests: NM, BC, NJ, and OB are employees of Akoya Biosciences. BH, advisory board member of Merck Sharpe and Dohme, Bristol Myers Squibb, Astra Zeneca, Pfizer, Takeda, Sanofi, Eisai. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Sadeghirad, Liu, Monkman, Ma, Cheikh, Jhaveri, Tan, Warkiani, Adams, Nguyen, Ladwa, Braubach, O’Byrne, Davis, Hughes and Kulasinghe.)
Databáze:	MEDLINE
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