Orchestration of B and T cells predicts prolonged survival after cancer immune checkpoint inhibitor therapy

Tertiary lymphoid structures (TLSs) facilitate tumor microenvironment immune interactions. While TLSs and their associated gene signatures correlate with better response to immune checkpoint inhibitors (ICIs), the complex transcriptomic interplay/co-regulation among these factors remains under investigation. We analyzed correlations between survival and transcriptome expression (35 immunoregulatory factors associated with B/T cells and TLSs) in 217 patients with ICI-treated solid tumors. Denser correlations among B/T cell markers, immune checkpoints, and TLS-related molecules was associated with longer survival. High CXCL13 (B-lymphocyte chemoattractant) expression correlated with longer overall survival (hazard ratio [HR] 0.46 [95% CI: 0.27-0.81], p = 0.006) in 217 ICI-treated patients but not in 272 ICI-naïve patients (HR 0.85 [0.52-1.40], p = 0.519), suggesting its potential predictive/ICI-related, rather than prognostic, value. Overall, patients with highly coordinated T- and B-cell activity, checkpoints, and TLS-related molecules, and higher CXCL13 expression demonstrated prolonged survival after ICIs. Comprehensive multiomics and tumor immunomic profiling may better predict outcome after immunotherapy.