Harnessing and Enhancing Macrophage Phagocytosis for Cancer Therapy

• Published in: Frontiers in immunology Vol. 12; p. 635173
• Main Authors: Chen, Siqi, Lai, Seigmund W T, Brown, Christine E, Feng, Mingye
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 10.03.2021
• Subjects: Adaptive Immunity - drug effects; Animals; Antibodies, Bispecific - adverse effects; Antibodies, Bispecific - therapeutic use; antibody; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; cancer immunotherapy; chimeric antigen receptor (CAR); Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunity, Innate - drug effects; Immunology; Immunotherapy, Adoptive - adverse effects; macrophage; nanoparticle; Nanoparticles; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; phagocytosis; Phagocytosis - drug effects; Phenotype; Receptors, Chimeric Antigen - genetics; Receptors, Chimeric Antigen - immunology; Receptors, Chimeric Antigen - metabolism; Tumor Microenvironment; Tumor-Associated Macrophages - drug effects; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; Tumor-Associated Macrophages - transplantation; chimeric antigen receptor (CAR); phagocytosis; macrophage; nanoparticle; antibody; cancer immunotherapy
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.635173

Cancer immunotherapy has revolutionized the paradigm for the clinical management of cancer. While FDA-approved cancer immunotherapies thus far mainly exploit the adaptive immunity for therapeutic efficacy, there is a growing appreciation for the importance of innate immunity in tumor cell surveillance and eradication. The past decade has witnessed macrophages being thrust into the spotlight as critical effectors of an innate anti-tumor response. Promising evidence from preclinical and clinical studies have established targeting macrophage phagocytosis as an effective therapeutic strategy, either alone or in combination with other therapeutic moieties. Here, we review the recent translational advances in harnessing macrophage phagocytosis as a pivotal therapeutic effort in cancer treatment. In addition, this review emphasizes phagocytosis checkpoint blockade and the use of nanoparticles as effective strategies to potentiate macrophages for phagocytosis. We also highlight chimeric antigen receptor macrophages as a next-generation therapeutic modality linking the closely intertwined innate and adaptive immunity to induce efficacious anti-tumor immune responses.