Core Viewpoint - The article discusses a breakthrough in cancer immunotherapy through the development of a trispecific antibody that enhances anti-tumor immunity by engaging T cells, tumor cells, and macrophages simultaneously, thus addressing the challenges posed by immune-suppressive tumor microenvironments [2][3][11]. Group 1 - The research team developed a trispecific antibody, B7H3×CD3×PDL1, which activates abundant bystander T cells instead of relying on rare tumor-specific T cells [3][6]. - The study proposes a new strategy that transforms macrophages from being viewed as obstacles to becoming facilitators of immune response [3][8]. - The trispecific T-cell engager (TriTCE) employs a tiered affinity design to create a "dynamically accessible" multi-cellular cooperative model, showing significant efficacy in various tumor models [6][9]. Group 2 - The mechanism analysis reveals that PDL1 plays a new role in the trispecific structure, acting as a key hub to bring PDL1+ macrophages closer to activated T cells [8][9]. - The strategy can achieve anti-tumor effects even in immune-cold tumors with very few T cells, demonstrating an "overcoming the odds" capability [9][11]. - The research integrates cross-cancer clinical cohort data and transcriptional data to build a machine learning model that predicts patient responses, aiding in the identification of suitable candidates for future trispecific antibody therapies [11].