Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils

Abstract

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors.

CAR-based immunotherapy for breast cancer: peculiarities, ongoing investigations, and future strategies

“…Based on the specificity of CAR, CAR-M results in antigenspecific phagocytosis and tumor clearance (26,165). CAR-Ms express pro-inflammatory cytokines and chemokines, resulting in the transition of M2 macrophages into a pro-inflammatory (M1) phenotype, induction of a pro-inflammatory TME, and resistance to the effects of immunosuppressive cytokines (155).…”