Work

Spatial heterogeneity and prognostic value of tertiary lymphoid structures in peritumoral inflammation and tumor beds after neoadjuvant immunochemotherapy for resectable NSCLC

Year: 2026

Type: article

Abstract: Tertiary lymphoid structures (TLS) are associated with favorable outcomes in non-small cell lung cancer (NSCLC) following neoadjuvant immunochemotherapy. However, the biological and prognostic differences between TLS in peritumoral inflammation (PI) and the tumor bed (TB) remain unclear. We analyzed 254 patients with NSCLC from three centers: 98 treated with neoadjuvant immunochemotherapy (NICT), 54 treated with neoadjuvant chemotherapy (NCT), and 102 treatment-naïve patients. PI and TB TLS abundance and maturation were assessed in relation to pathological response and survival. Exploratory spatial transcriptomics characterized their cellular composition and intercellular communication. PI was more prevalent in the NICT cohort (77.5%) than in the NCT (50.0%) and treatment-naïve (26.5%) cohorts ( p < 0.001). In the NICT cohort, PI TLS were more abundant and mature than TB TLS. Multivariable analysis showed that PI-related TLS were independently associated with recurrence-free survival (RFS) after adjustment for major pathological response, TB TLS abundance, and other clinicopathological factors. A nomogram incorporating ypN stage and PI-related features achieved areas under the curve (AUCs) of 0.894, 0.884, and 0.887 for predicting 1-, 2-, and 3-year RFS, respectively. Spatial transcriptomics revealed distinct transcriptional and immune profiles, with PI TLS showing greater plasma cell abundance and more active interactions with the tumor microenvironment than TB TLS. In resectable NSCLC, NICT was associated with a higher prevalence of PI and greater TLS abundance and maturation. PI TLS showed greater prognostic value and a more immune-active microenvironment than TB TLS, supporting spatial TLS assessment for postoperative risk stratification.

Source: Cellular Oncology

DOI: 10.1007/s13402-026-01287-2