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-Bermudez, Alberto
A1 Nadal, Ernest
A1 Insa, Amelia
A1 Garcia Campelo, Maria del Rosario
A1 Lazaro, Martin
A1 Domine, Manuel
A1 Majem, Margarita
A1 Rodriguez-Abreu, Delvys
A1 Martinez-Marti, Alex
A1 de Castro-Carpeno, Javier
A1 Cobo, Manuel
A1 Lopez-Vivanco, Guillermo
A1 Del Barco, Edel
A1 Bernabe Caro, Reyes
A1 Vinolas, Nuria
A1 Barneto Aranda, Isidoro
A1 Viteri, Santiago
A1 Massuti, Bartomeu
A1 Barquin, Miguel
A1 Laza-Briviesca, Raquel
A1 Sierra-Rodero, Belen
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
K1 Blockade
K1 Chemotherapy
K1 Dynamics
K1 Tumor
AB 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 nonsmall 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 nonCPR. Beyond TCR metrics, tissue clones were ranked by their frequency and spatiotemporal evolution of top 1% clones was determined.Results: Wehave 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.
PB Amer assoc cancer research
SN 1078-0432
YR 2021
FD 2021-11-01
LK https://hdl.handle.net/10668/25720
UL https://hdl.handle.net/10668/25720
LA en
DS RISalud
RD Apr 5, 2025