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
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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