دورية أكاديمية
أعرض في EDS

DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma.

التفاصيل البيبلوغرافية
العنوان: DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma.
المؤلفون: Starzer AM; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Heller G; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Tomasich E; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Melchardt T; Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Paracelsus Medical University Salzburg, Salzburg, Austria., Feldmann K; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Hatziioannou T; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Traint S; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria., Minichsdorfer C; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria., Schwarz-Nemec U; Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria., Nackenhorst M; Department of Pathology, Medical University of Vienna, Vienna, Austria., Müllauer L; Department of Pathology, Medical University of Vienna, Vienna, Austria., Preusser M; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Berghoff AS; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria anna.berghoff@meduniwien.ac.at.; Department of Medicine I, Christian Doppler Laboratory for Personalized Immunotherapy, Medical University of Vienna, Vienna, Austria., Fuereder T; Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2022 Mar; Vol. 10 (3).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: Print Cited Medium: Internet ISSN: 2051-1426 (Electronic) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مواضيع طبية MeSH: B7-H1 Antigen*/metabolism , Head and Neck Neoplasms*/drug therapy , Head and Neck Neoplasms*/genetics, Aged ; Aged, 80 and over ; DNA Methylation ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Squamous Cell Carcinoma of Head and Neck/genetics ; Tumor Microenvironment
مستخلص: Background: Biomarkers for response prediction to anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) are urgently needed for a personalized therapy approach. We investigated the predictive potential of inflammatory parameters and DNA methylation profiling in patients with HNSCC treated with anti-PD-1 ICI.
Methods: We identified patients with HNSCC that were treated with anti-PD-1 ICI therapy in the recurrent or metastatic setting after progression to platinum-based chemotherapy in two independent centers. We analyzed DNA methylation profiles of >850.000 CpG sites in tumor specimens of these patients by Infinium MethylationEPIC microarrays, immune cell density in the tumor microenvironment (CD8, CD3, CD45RO, forkhead box P3 (FOXP3), CD68), PD-1 and programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry, and blood inflammation markers (platelet-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio). DNA methylation profiles and immunological markers were bioinformatically and statistically correlated with radiological response to anti-PD-1 ICI.
Results: 37 patients with HNSCC (median age of 62 years; range 49-83; 8 (21.6%) women, 29 (78.4%) men) were included (Center 1 N=26, 70.3%; Center 2 N=11, 29.7%). Median number of prior systemic therapies was 1 (range 1-4). Five out of 37 (13.5%) patients achieved an objective response to ICI. Median progression-free survival and median overall survival times were 3.7 months (range 0-22.9) and 9.0 months (range 0-38.8), respectively. Microarray analyses revealed a methylation signature including both hypomethylation and hypermethylation which was predictive for response to ICI and included several genes involved in cancer-related molecular pathways. Over-represented differentially methylated genes between responders and non-responders were associated with 'Axon guidance', 'Hippo signaling', 'Pathways in cancer' and 'MAPK signaling'. A statistically significant correlation of PD-L1 expression and response was present (p=0.0498).
Conclusions: Our findings suggest that tumor DNA methylation profiling may be useful to predict response to ICI in patients with HNSCC.
Competing Interests: Competing interests: AS has received travel support from PharmaMar. ASB has research support from Daiichi Sankyo and Roche, honoraria for lectures, consultation or advisory board participation from Roche Bristol Meyers Squibb, Merck, Daiichi Sankyo as well as travel support from Roche, Amgen, Daiichi Sankyo and AbbVie. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen. The following for-profit companies have supported clinical trials and contracted research conducted by MP with payments made to his institution: Böhringer-Ingelheim, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dome, Novocure, GlaxoSmithKline, AbbVie.
(© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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فهرسة مساهمة: Keywords: Biomarkers, Tumor; Head and Neck Neoplasms; Immunotherapy; Translational Medical Research; Tumor Microenvironment
المشرفين على المادة: 0 (B7-H1 Antigen)
0 (Immune Checkpoint Inhibitors)
0 (Programmed Cell Death 1 Receptor)
تواريخ الأحداث: Date Created: 20220326 Date Completed: 20220414 Latest Revision: 20220712
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC8961155
DOI: 10.1136/jitc-2021-003420
PMID: 35338086
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1136/jitc-2021-003420