Characterization of Circulating T Cell Receptor Repertoire Provides Information about Clinical Outcome after PD-1 Blockade in Advanced Non-Small Cell Lung Cancer Patients
Por:
N. DONG, A. MORENO-MANUEL, S. CALABUIG-FARINAS, S. GALLACH, F. ZHANG, A. BLASCO, F. APARISI, M. MERI-ABAD, R. GUIJARRO, R. SIRERA, C. CAMPS and E. JANTUS-LEWINTRE
Publicada:
1 jun 2021
Resumen:
Simple Summary Immune checkpoint blockers (ICBs) have demonstrated durable anti-tumor responses in advanced non-small cell lung cancer (NSCLC). Despite progress in development of new predictive biomarkers, such as PD-L1 expression, TMB, or MSI, there is still an urge for a better selection of patients that will benefit from the blockade of PD-1/PD-L1 axis. In this study, peripheral blood T cell receptor beta chain (TCR-beta) repertoire, at baseline (PRE) and first response (FR) assessment, was analyzed with high-throughput sequencing in a cohort of advanced NSCLC patients receiving first-line pembrolizumab. Our results suggest that measuring TCR-beta features in peripheral blood may be a potential tool to assess patients' immune response. Furthermore, the usage of the TRBV20-1 segment highly predicts host response and survival in anti-PD-1 treated NSCLC patients. Despite the success of immunotherapies in lung cancer, development of new biomarkers for patient selection is urgently needed. This study aims to explore minimally invasive approaches to characterize circulating T cell receptor beta chain (TCR-beta) repertoire in a cohort of advanced non-small cell lung cancer (NSCLC) patients treated with first-line pembrolizumab. Peripheral blood samples were obtained at two time points: i) pretreatment (PRE) and ii) first response assessment (FR). Next-generation sequencing (NGS) was used to analyze the hypervariable complementary determining region 3 (CDR3) of TCR-beta chain. Richness, evenness, convergence, and Jaccard similarity indexes plus variable (V) and joining (J)-gene usage were studied. Our results revealed that increased richness during treatment was associated with durable clinical benefit (DCB; p = 0.046), longer progression-free survival (PFS; p = 0.007) and overall survival (OS; p = 0.05). Patients with Jaccard similarity index >= 0.0605 between PRE and FR samples showed improved PFS (p = 0.021). Higher TRBV20-1 PRE usage was associated with DCB (p = 0.027). TRBV20-1 levels >= 9.14% in PRE and >= 9.02% in FR significantly increased PFS (p = 0.025 and p = 0.016) and OS (p = 0.035 and p = 0.018). Overall, analysis of circulating TCR-beta repertoire may provide information about the immune response in anti-PD-1 treated NSCLC patients; in this scenario, it can also offer important information about the clinical outcome.
Filiaciones:
N. DONG:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Univ Valencia, Dept Pathol, Valencia 46010, Spain
S. GALLACH:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
F. ZHANG:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
A. BLASCO:
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
F. APARISI:
Hosp Gen Requena, Dept Med Oncol, Valencia 46340, Spain
M. MERI-ABAD:
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
R. GUIJARRO:
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Univ Valencia, Dept Surg, Valencia 46010, Spain
Hosp Gen Univ Valencia, Dept Thorac Surg, Valencia 46014, Spain
R. SIRERA:
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia 46022, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Hosp Gen Univ Valencia, Dept Med Oncol, Valencia 46014, Spain
Univ Valencia, Dept Med, Valencia 46010, Spain
:
Hosp Gen Univ Valencia, Fdn Invest, Mol Oncol Lab, Valencia 46014, Spain
Hosp Gen Univ Valencia, Ctr Invest Principe Felipe, Fdn Invest, Unidad Mixta TRIAL, Valencia 46014, Spain
Ctr Invest Biomed Red Canc, CIBERONC, Madrid 28029, Spain
Univ Politecn Valencia, Dept Biotechnol, Valencia 46022, Spain
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