Natural polysaccharide riclin acts as an immune adjuvant to enhance chemotherapy efficacy in NSCLC.

Chemotherapy-induced immunosuppression compromises therapeutic outcomes in oncology, particularly in non-small cell lung cancer (NSCLC). While natural polysaccharides have emerged as promising candidates to counteract drug-related immunosuppression, the therapeutic potential of riclin remains unexplored in chemotherapeutic contexts. Here, we systematically evaluated riclin's immunoadjuvant efficacy in a murine NSCLC model treated with gemcitabine (GEM). Oral riclin modulated gut microbiota diversity and metabolite profiles while activating the immune-hematopoietic axis, thereby boosting immunity and hematopoiesis. Mechanistically, riclin counteracted GEM-induced immunosuppression through coordinated NF-κB and JAK-STAT activation, as evidenced by the restoration of circulating immune cells and splenic architecture, expansion of bone marrow mononuclear cells (BMNCs) and Lineage⁻Sca-1⁺Kit⁺ (LSK) cells, and suppression of apoptosis. Notably, riclin demonstrated synergistic effects with GEM, achieving 98% tumor burden reduction while concurrently alleviating systemic immunosuppression. We propose that riclin, a novel oral immunoadjuvant capable of enhancing chemotherapeutic efficacy in NSCLC, supports its clinical development as a promising combination strategy.