Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non-small-cell lung carcinoma
Autor: | Véronique Duchatelle, Diane Damotte, Y. Velut, R. Herbst, Ludovic Fournel, G. Boulle, Scott A. Hammond, M. Wislez, Isabelle Cremer, Laure Gibault, Philippe Giraud, Hélène Blons, Marco Alifano, Audrey Mansuet-Lupo, A. Boni, Jean Trédaniel |
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Přispěvatelé: | Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris (UP), Sorbonne Université (SU), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre hospitalier Saint-Joseph [Paris], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CCSD, Accord Elsevier |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Time Factors medicine.medical_treatment T cell [SDV]Life Sciences [q-bio] Population CD8-Positive T-Lymphocytes B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Lymphocytes Tumor-Infiltrating Internal medicine Carcinoma Non-Small-Cell Lung medicine Carcinoma Tumor Microenvironment Humans education Lung cancer Aged Neoplasm Staging Retrospective Studies Aged 80 and over education.field_of_study business.industry Abscopal effect Forkhead Transcription Factors Chemoradiotherapy Chemoradiotherapy Adjuvant Middle Aged medicine.disease 3. Good health [SDV] Life Sciences [q-bio] Radiation therapy 030104 developmental biology medicine.anatomical_structure Treatment Outcome 030220 oncology & carcinogenesis Immunogenic cell death Female business |
Zdroj: | European Journal of Cancer European Journal of Cancer, Elsevier, 2020, 135, pp.221-229. ⟨10.1016/j.ejca.2020.04.040⟩ European Journal of Cancer, 2020, 135, pp.221-229. ⟨10.1016/j.ejca.2020.04.040⟩ |
ISSN: | 1879-0852 0959-8049 |
Popis: | Background Radiotherapy is a standard of care for locally advanced stage III N2 non–small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival. Patients and methods We retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival. Results High density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99–3.78]) and DFS (p = 0.003, HR = 2.42 [1.31–4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11–3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98–3.74]) and PFS (p = 0.03, HR = 1.83 [1.03–3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1–49%) was associated with a higher survival in the PORT. Conclusions Intra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy. |
Databáze: | OpenAIRE |
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