Artículo
Pretreatment tissue TCR repertoire evenness is associated with complete pathologic response in patients with NSCLC receiving neoadjuvant chemoimmunotherapy
Autor/es | Casarrubios, Marta
Cruz-Bermúdez, Alberto Nadal, Ernest Insa, Amelia del Rosario García Campelo, María Lázaro, Martín Dómine, Manuel Caro, Reyes Bernabé Provencio, Mariano |
Departamento | Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2021 |
Fecha de depósito | 2022-09-27 |
Publicado en |
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Resumen | Purpose: Characterization of the T-cell receptor (TCR) reper-
toire may be a promising source for predictive biomarkers of
pathologic response to immunotherapy in locally advanced non–
small cell lung cancer ... Purpose: Characterization of the T-cell receptor (TCR) reper- toire 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 sam- ples 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 ¼ 0.001), and improving the results of PD-L1 tumor proportion score (TPS; AUC ¼ 0.767; P ¼ 0.026) or tumor mutational burden (TMB; AUC ¼ 0.550; P ¼ 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 selec- tive expansion of pretreatment tissue top 1% clones in peripheral blood of CPR patients suggests also a peripheral immunosurveil- lance, 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. |
Cita | Casarrubios, M., Cruz-Bermúdez, A., Nadal, E., Insa, A., del Rosario García Campelo, M., Lázaro, M.,...,Provencio, M. (2021). Pretreatment tissue TCR repertoire evenness is associated with complete pathologic response in patients with NSCLC receiving neoadjuvant chemoimmunotherapy. Clinical Cancer Research, 27 (21), 5878-5890. |