背靠背两篇Cancer Cell：靶向巨噬细胞的CAR-T细胞疗法，重塑肿瘤微环境，广谱治疗实体瘤

Core Viewpoint - The articles highlight the potential of CAR-T cell therapies targeting tumor-associated macrophages (TAM) expressing IL-12, which can reshape the tumor microenvironment and stimulate anti-tumor immune responses against solid tumors, independent of tumor antigens [3][7][12]. Group 1: Research Findings - The study from Mount Sinai Icahn School of Medicine developed IL-12 armored CAR-T cells targeting FOLR2 or TREM2 to eliminate pro-tumor TAMs, significantly improving survival rates in metastatic ovarian and lung cancer models [5][10]. - The CAR-T therapy demonstrated efficacy at low cell doses without the need for lymphocyte depletion, primarily localized to tumor sites with no significant side effects [5][10]. - Spatial transcriptomics indicated that the CAR-T cells could continue to reshape the tumor microenvironment even after their numbers naturally declined post-treatment, leading to the expansion of immune-stimulating macrophages and endogenous tumor-specific cytotoxic T cells [5][10]. Group 2: Mechanism and Strategy - The research introduced a CAR targeting TREM2+ immunosuppressive TAMs, showing strong in vitro activity and significant anti-tumor effects in vivo [10]. - A synthetic CAR-responsive biosensor was incorporated to enhance local IL-12 secretion within the tumor, further improving the therapeutic effect [10]. - The IL-12 armored hTREM2 CAR-T cells reprogrammed the tumor microenvironment and lymph nodes, clearing TREM2+ TAMs and enhancing the infiltration and activation of T cells and natural killer (NK) cells, leading to tumor regression without systemic toxicity [10][12].