Impact of platinum-based chemotherapy on the tumor mutational burden and immune microenvironment in non-small cell lung cancer with postoperative recurrence.

PURPOSE: To investigate the impact of platinum-based adjuvant chemotherapy on the immunotherapeutic biomarkers of postoperative recurrent tumors in non-small cell lung cancer (NSCLC).

METHODS

This study involved twenty-two cases of NSCLC, all of which underwent postoperative platinum-based chemotherapy, with matched surgical samples obtained from both their primary tumors (PTs) and recurrent tumors (RTs). Multiplex immunofluorescence was performed to assess the tumor proportion score (TPS) and immune cells (IC) on whole sections. Whole exon sequencing (WES) was conducted to investigate the tumor mutational burden (TMB) and tumor neoantigen burden (TNB).

RESULTS

Compared to paired PTs, RTs exhibited higher PD-L1 expression, along with a slightly elevated density of intratumoral PD-L1+ cells (p = 0.082) and an increased tumor proportion score (mean TPS: 40.51% vs. 28.56%, p = 0.046). Regarding IC infiltration, RTs generally demonstrated significantly lower CD8+  cytotoxic T lymphocyte (CTL) density (p = 0.011) and lower CD68+  macrophage density (p = 0.005), with a loss of tertiary lymphoid structure (TLS). The comparison between RTs and PTs revealed no significant differences in TMB (p = 0.795), whereas the count of TNB in RTs was notably increased compared to PTs (p = 0.033). Prognosis analysis indicated that a higher density of CD8+  CTLs in RTs was positively correlated with improved overall survival (OS).

CONCLUSIONS

In NSCLC patients with a history of postoperative platinum-based chemotherapy, the RTs demonstrated a trend towards increased PD-L1 expression and TMB/TNB, but a state of immunosuppression characterized by decreased ICs and loss of TLS, which may potentially impact the therapeutic benefits of immunotherapy.