Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
| Autor: | Alex Martinez-Marti, Edwin R. Parra, Bartomeu Massuti, Manuel Domine, Manuel Cobo, M. Lázaro, Nuria Viñolas, Pedro Rocha, Edel del Barco, Guillermo Lopez-Vivanco, Reyes Bernabe Caro, Miguel Barquín, Mariano Provencio, Santiago Viteri, Raquel Laza-Briviesca, Belén Sierra-Rodero, Alberto Cruz-Bermúdez, Ignacio I. Wistuba, Isidoro Barneto Aranda, Amelia Insa, Humam Kadara, Maria Rosario Garcia Campelo, Margarita Majem, M. Casarrubios, Delvys Rodriguez-Abreu, Ernest Nadal, Beatriz Sanchez-Espiridion, Javier de Castro-Carpeño, Virginia Calvo, Atocha Romero |
|---|---|
| Přispěvatelé: | Institut Català de la Salut, [Casarrubios M, Cruz-Bermúdez A] Servicio de Oncología Médica, Instituto de Investigacion Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain. [Nadal E] Institut Català d’Oncologia, L’Hospitalet de Llobregat, L’Hospitalet De Llobregat, Barcelona, Spain. [Insa A] Fundacion INCLIVA, Hospital Clínico Universitario de Valencia, Valencia, Spain. [García Campelo MDR] Hospital Universitario A Coruna, A Coruña, Spain. [Lázaro M] Hospital Universitario de Vigo, Pontevedra, Spain. [Martínez-Martí A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Cèl·lules T - Receptors Male Cancer Research medicine.medical_specialty aminoácidos péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de antígenos::receptores de antígenos de linfocitos T [COMPUESTOS QUÍMICOS Y DROGAS] Lung Neoplasms medicine.medical_treatment Receptors Antigen T-Cell Immune system Chemoimmunotherapy Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans Prospective Studies Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors Immunologic::Receptors Antigen::Receptors Antigen T-Cell [CHEMICALS AND DRUGS] Otros calificadores::/terapia [Otros calificadores] Aged business.industry Immunogenicity T-cell receptor High-Throughput Nucleotide Sequencing Immunotherapy Other subheadings::/therapy [Other subheadings] Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma Bronchogenic::Carcinoma Non-Small-Cell Lung [DISEASES] neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES] Middle Aged Neoadjuvant Therapy Peripheral Immunosurveillance Clinical trial Treatment Outcome Avaluació de resultats (Assistència sanitària) Female business Pulmons - Càncer - Tractament |
| Zdroj: | Scientia CLINICAL CANCER RESEARCH r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose:Characterization of the T-cell receptor (TCR) repertoire may be a promising source for predictive biomarkers of pathologic response to immunotherapy in locally advanced non–small cell lung cancer (NSCLC).Experimental Design:In this study, next-generation TCR sequencing was performed in peripheral blood and tissue samples of 40 patients with NSCLC, before and after neoadjuvant chemoimmunotherapy (NADIM clinical trial, NCT03081689), considering their complete pathologic response (CPR) or non-CPR. Beyond TCR metrics, tissue clones were ranked by their frequency and spatiotemporal evolution of top 1% clones was determined.Results:We have found a positive association between an uneven TCR repertoire in tissue samples at diagnosis and CPR at surgery. Moreover, TCR most frequently ranked clones (top 1%) present in diagnostic biopsies occupied greater frequency in the total clonal space of CPR patients, achieving an AUC ROC to identify CPR patients of 0.967 (95% confidence interval, 0.897–1.000; P = 0.001), and improving the results of PD-L1 tumor proportion score (TPS; AUC = 0.767; P = 0.026) or tumor mutational burden (TMB; AUC = 0.550; P = 0.687). Furthermore, tumors with high pretreatment top 1% clonal space showed similar immune cell populations but a higher immune reactive gene expression profile. Finally, the selective expansion of pretreatment tissue top 1% clones in peripheral blood of CPR patients suggests also a peripheral immunosurveillance, which could explain the high survival rate of these patients.Conclusions:We have identified two parameters derived from TCR repertoire analysis that could outperform PD-L1 TPS and TMB as predictive biomarkers of CPR after neoadjuvant chemoimmunotherapy, and unraveled possible mechanisms of CPR involving enhanced tumor immunogenicity and peripheral immunosurveillance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|