Fig. 8. Summary of key anti-tumor events occurring during neoadjuvant chemoimmunotherapy.

Neoadjuvant chemoimmunotherapy promotes LAMP3⁺ DCs aggregation in tumor lesions, and the increased LAMP3⁺ DCs acquire tumor antigen, migrate and interact with lymphocytes, and participate in the activation, recruitment, and regulation of T/B lymphocytes through L-R interactions. Anti-PD-1 therapy reinvigorates the expansion of intratumoral CD4⁺ T cells and peripheral cytotoxic CD8⁺ T clones and promoted CD8⁺ T cells migration to tumor tissues to exert an anti-tumor effect. Neoadjuvant chemoimmunotherapy promotes more TLSs formation in NSCLC tumor tissues. In tumor-associated TLSs, IL-21 secreted by Tfh cells promotes B cells class switching to IgG1 and IgG3 but not IgA to mediate anti-tumor response. IgG1 and IgG3 antibodies bind to Fcγ receptor (FcγR) and trigger ADCC and antibody-mediated phagocytosis and mediate complement-based cytotoxicity. In addition, the decrease of immunosuppressive IgA⁺plasma cells and TNFRSF4⁺ Tregs lead to the repression of immunosuppression during chemoimmunotherapy.