This review highlights the critical role of tumor-associated macrophages (TAMs) in affecting CAR-T cell therapy effectiveness in solid tumors. TAMs contribute to immune suppression through cytokine secretion, immune checkpoint activation, and metabolic reprogramming, leading to CAR-T cell exhaustion and reduced efficacy. The article explores strategies to counteract TAM-driven immune evasion and improve CAR-T cell outcomes in solid tumors.
Abstract
Although CAR T-cell therapy has transformed treatment outcomes for patients with haematological malignancies, the existing barriers in solid tumors treatment remain due to TAM immunosuppression. This review explores the work of others on the interplay between M2-like immunosuppressive TAMs and CAR-T cells in the tumor microenvironment. The ways TAMs impair the effector functions of CAR-T cells are described mediated by secretion of cytokines, immune checkpoints, metabolites, and detrimental post-translational modification. New concept therapeutic approaches are designed to these interactions for improving the efficacy of CAR-T cells in solid tumors. With an emphasis on novel strategies to counteract TAM immunosuppression, this review aims to reshape the perspective on the utility and effectiveness of CAR-T therapy in solid tumors and, consequently, extend the reach of a highly promising therapeutic approach.
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