Blood T cell diversity associated with the prognosis of advanced non‐small cell lung carcinoma treated with first‐line pemetrexed based chemotherapy

Abstract

Abstract Background The tumor microenvironment is associated with prognosis in advanced non‐small cell lung carcinoma (NSCLC). The aim of this study was to explore the relationship between blood T cell diversity and survival of patients treated with pemetrexed‐based chemotherapy for nonsquamous NSCLC. Methods This prospective clinical study enrolled 26 patients with advanced NSCLC treated with 4–6 cycles of first‐line pemetrexed combined with platinum‐based therapy. The complementarity‐determining region 3 (CDR3) located in the T cell receptor beta chain (TCR β chain) was captured and deeply sequenced using next‐generation sequencing (NGS) technology, and the correlation between TCR changes and efficacy after chemotherapy was analyzed. Results Patients with an inferior quarter diversity index showed a significantly shorter progression‐free survival (PFS) than the others (median, 5.0 months vs. 8.1 months, P = 0.014). After two cycles of chemotherapy, the TCR diversity was significantly higher than the baseline (P = 0.034). Just as with the baseline, patients with an inferior quarter diversity index at the endpoint of cycle 2 showed a shorter progression‐free survival (PFS) than the others (median, 5.0 months vs. 8.4 months, P = 0.024). Conclusions In advanced NSCLC patients treated with first‐line pemetrexed combined with platinum, the low level of blood TCR diversity at baseline with an endpoint of two cycles of chemotherapy was correlated with a poor prognosis.

Keywords

• Advanced non‐small cell lung carcinoma
• T cell diversity
• tumor microenvironment