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

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.

Figure 1

Diversity and prognosis. The relationship between diversity Shannon index and prognosis at (a) baseline () >6.21(18) () <6.21(7); (b) after two cycles () >6.66(15) () <6.66(7); (c) after four cycles () > () 6.87(8) () <6.87(4) and (d) after six cycles () >5.91(4) () <5.91(2).

Figure 2

The diversity change between (a) baseline and after two cycles; (b) between after two and after four cycles; and (c) between baseline and after four cycles.

Figure 3

(a) The diversity changes of the eight EGFR exon 19 deletion mutation patients () P001 () P003 () P011 () P012 () P020 () P024 () P026 () P027. (b) Differences of PFS (5.7 months vs. 8.4 months, P = 0.328); and (c) DepOR (−0.298 vs.−0.3647, P = 0.600) between EGFR exon 19 deletion mutation patients and EGFR‐wt patients () EGFR+ () EGFR‐.

Figure 4

Diversity change of three patients treated by immunotherapy and CT performance of patient No. 025. (a) Chest image at baseline. (b) Chest image after two cycles. (c) Chest image after four cycles. (d) Chest image after six cycles. (e) Chest image after two cycles of monoimmunotherapy. (f) Diversity change of the three patients treated by immunotherapy () P008 () P023 () P025.