Intratumoral Injection of R848 and Poly(I:C) Synergistically Promoted Antitumour Immune Responses by Reprogramming Macrophage Polarization and Activating DCs in Lung Cancer

Immunotherapy has rapidly become a primary treatment option for many lung cancer patients because of its success in treating this prevalent and deadly disease. However, the success of immunotherapy relies on overcoming the immunosuppressive tumour microenvironment, making remodelling this environment a potential strategy for lung cancer therapy. Research suggests that Toll-like receptor (TLR) agonists can impede tumour growth by promoting the conversion of tumour-associated macrophages into an M1-like state or enhancing dendritic cell development. However, there is insufficient research on the combined use of TLR agonists for treating lung cancer. In this study, we examined how TLR agonists such as resiquimod (R848) and poly(I:C) impact lung cancer treatment when used alone or in combination. In vitro, the regulatory functions and mechanisms of R848 and poly(I:C) were analysed in primary macrophages, RAW264.7 cells, and primary dendritic cells(DCs). Tumour treatment efficacy was assessed in vivo with a Lewis lung carcinoma (LLC) mouse model. The combination of R848+poly(I:C) enhances the transformation of macrophages from the M2 phenotype to the M1 phenotype by increasing inflammatory cytokine levels. The percentage of mature DCs expressing MHC-II+CD11c+ and CD86+ cells was significantly higher in the R848+poly(I:C) group compared with the other groups. Intratumoral injection of the synergistic combination of R848+poly(I:C) suppressed tumour growth by increasing the M1:M2 ratio in TAMs, activating DCs, and attracting CD4+ and CD8+ T cells. R848+poly(I:C) synergistically induce M1-like polarization of macrophages, activate DCs, and promote effective antitumour immunity in mice with subcutaneous LLC tumours.