دورية أكاديمية
Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111-24111).
| العنوان: | Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111-24111). |
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| المؤلفون: | Beyaert SP; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium., Loriot AE; Group of Computational Biology and Bioinformatics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium., Huyghe ND; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium., Goebbels RM; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium., Mendola A; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium., Govaerts AS; European Organization of Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium., Fortpied C; European Organization of Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium., Baldin P; Department of Pathology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium., Licitra LF; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; University of Milan, Milan, Italy., Lalami Y; Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium., Clement PM; Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium., Machiels JH; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium.; Department of Medical Oncology, Institut Roi Albert II & Cliniques Universitaires Saint-Luc, Brussels, Belgium., Schmitz S; Institut de Recherche Expérimentale et Clinique (IREC), pôle MIRO, Université catholique de Louvain (UCLouvain), Brussels, Belgium.; Department of Head & Neck Surgery, Institut Roi Albert II & Cliniques Universitaires Saint-Luc, Brussels, Belgium. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Oct 13; Vol. 29 (20), pp. 4076-4087. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مستخلص: | Purpose: The EORTC-90111-24111 phase II window study evaluated afatinib versus no preoperative treatment in patients with primary squamous cell carcinoma of the head and neck (HNSCC). We investigated afatinib-induced tumor and microenvironment modifications by comparing pre- and posttreatment tumor biopsies. Patients and Methods: Thirty treatment-naïve patients with primary HNSCC were randomized. Twenty-five patients received afatinib for 14 days before surgery (40 mg 1×/day) and 5 patients were attributed to the control arm. Biopsies were taken at work-up and during surgery. Good quality RNA samples were used for omics analyses. The control arm was enlarged by samples coming from our previous similar window study. Results: IHC analyses of afatinib-treated tumor biopsies showed a decrease in pEGFR (P ≤ 0.05) and pERK (P ≤ 0.05); and an increase in CD3+ (P ≤ 0.01) and CD8+ (P ≤ 0.01) T-cell infiltration, and in CD3+ (P ≤ 0.05) T-cell density. RNA sequencing analyses of afatinib-treated tumor samples showed upregulation of inflammatory genes and increased expression scores of signatures predictive of response to programmed cell death protein 1 blockade (P ≤ 0.05). In posttreatment biopsies of afatinib-treated patients, two clusters were observed. Cluster 1 showed a higher expression of markers and gene sets implicated in epithelial-to-mesenchymal transition (EMT) and activation of cancer-associated fibroblasts (CAF) compared with cluster 2 and controls. Conclusions: Short-term treatment with afatinib in primary HNSCC induces CD3+ and CD8+ tumor infiltration and, in some patients, EMT and CAF activation. These results open perspectives to overcome resistance mechanisms to anti-HER therapy and to potentiate the activity of immune checkpoint inhibitors. (©2023 American Association for Cancer Research.) |
| معلومات مُعتمدة: | Fondation Saint Luc (Fondation Saint-Luc); Fonds Spéciaux de Recherche (FSR); Keeping me Alive |
| تواريخ الأحداث: | Date Created: 20230802 Latest Revision: 20231013 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1158/1078-0432.CCR-23-0645 |
| PMID: | 37531234 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-23-0645 |