2026-04-05T12:50:55Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/76642024-12-13T10:45:32Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Casarrubios García, Marta
author
Cruz-Bermúdez, Alberto
author
Martínez Marti, Alexandre
author
Martínez Marti, Alexandre
author
Insa, Amelia
author
Nadal, Ernest
author
Lázaro, Martín
author
Garcia Campelo, Rosario
2023-11-08T10:18:32Z
2023-11-08T10:18:32Z
2022-06-13T09:57:37Z2022-06-13T09:57:37Z2021-11-01
http://hdl.handle.net/11351/7664
Neoadjuvant Chemoimmunotherapy; Lung cancer; T-cell receptorQuimioimmunoteràpia neoadjuvant; Càncer de pulmó; Receptor de cèl·lules TQuimioinmunoterapia neoadyuvante; Cáncer de pulmón; Receptor de células TPurpose:
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.
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
Pulmons - Càncer - Tractament
Cèl·lules T - Receptors
Avaluació de resultats (Assistència sanitària)
DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung
Other subheadings::Other subheadings::/therapy
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Antigen::Receptors, Antigen, T-Cell
ENFERMEDADES::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
Otros calificadores::Otros calificadores::/terapia
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores inmunológicos::receptores de antígenos::receptores de antígenos de linfocitos T
Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion