3M-052 combined inhibitory anti-TNFR2 synergistically suppresses colon cancer progression

Introduction Immunotherapy is considered the most promising approach for achieving complete tumor clearance in cancer treatment. However, monotherapy has demonstrated limited clinical efficacy, leading to a growing consensus that combination immunotherapy—activating the immune system through multiple pathways—appears to be the optimal strategy for enhancing therapeutic outcomes. In this study, we investigated the efficacy and underlying mechanisms of the combination immunotherapy MT—comprising the TLR7/8 agonist 3M-052 and the inhibitory anti-TNFR2 antibody—in colon cancer (CRC). Methods A CRC mouse model was established and divided into four treatment groups: the control group, the 3M-052 group, the anti-TNFR2 group, and the MT group. Tumour growth was monitored every three days. Flow cytometry was used to analyse the levels of CD8+ T cells and regulatory T cells (Tregs) in tumour tissue, as well as the differentiation of central memory T cells (Tcm) in the tumor-draining lymph nodes (TdLNs). Results The results revealed that the combination therapy MT promoted CD8+ T cell infiltration and reduced Tregs level within the tumor, effectively suppressed colon cancer growth in mice, and induced long-term syngeneic tumor control by enhancing the differentiation of Tcm in TdLNs. Compared with monotherapy, combination therapy MT demonstrated a superior capacity to induce the differentiation of central memory CD8+ and CD4+ T cells in TdLNs, an effect that appears to be primarily mediated by 3M-052. Discussion This study demonstrates that the combination of 3M-052 and the anti-TNFR2 antibody exerts a synergistic effect, effectively inhibiting CRC progression and inducing long-term immune memory. Overall, these findings support the view that MT combination therapy represents a potentially effective strategy.