RT Journal Article
T1 Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy.
A1 Casarrubios, Marta
A1 Cruz-Bermúdez, Alberto
A1 Nadal, Ernest
A1 Insa, Amelia
A1 García Campelo, María Del Rosario
A1 Lázaro, Martín
A1 Dómine, Manuel
A1 Majem, Margarita
A1 Rodríguez-Abreu, Delvys
A1 Martínez-Martí, Alex
A1 de Castro-Carpeño, Javier
A1 Cobo, Manuel
A1 López-Vivanco, Guillermo
A1 Del Barco, Edel
A1 Bernabé Caro, Reyes
A1 Viñolas, Nuria
A1 Barneto Aranda, Isidoro
A1 Viteri, Santiago
A1 Massuti, Bartomeu
A1 Barquín, Miguel
A1 Laza-Briviesca, Raquel
A1 Sierra-Rodero, Belén
A1 Parra, Edwin R
A1 Sanchez-Espiridion, Beatriz
A1 Rocha, Pedro
A1 Kadara, Humam
A1 Wistuba, Ignacio I
A1 Romero, Atocha
A1 Calvo, Virginia
A1 Provencio, Mariano
AB 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). 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. 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. 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.
YR 2021
FD 2021-08-10
LK https://hdl.handle.net/10668/25719
UL https://hdl.handle.net/10668/25719
LA en
DS RISalud
RD Apr 6, 2025