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Updated: Nov 7, 2025
Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Manipulating macrophage polarization in cancer patients: From nanoparticles to human chimeric antigen receptor
Matteo Santoni1, Francesco Massari2, Rodolfo Montironi3
1Oncology Unit, Macerata Hospital, via Santa Lucia 2, 62100 Macerata, Italy.
Abstract:
Chimeric antigen receptor (CAR) T cell treatment has provided notable results in hematological tumors. Unfortunately, this evidence has not been translated into improved outcomes in solid malignancies so far, where several reports have suggested that T cells encounter substantial difficulties in penetrating and surviving in the tumor microenvironment (TME). Thus, researchers have recently investigated other immune cell types as CAR platforms, in order to overcome the limitations of CAR T cells. Among them, CAR-macrophages (M) technology has emerged as a novel perspective for cancer patients, on the basis of preclinical studies observing that CAR expression in human macrophages could play a crucial role in enhancing phagocytosis, polarizing M2 to M1 phenotype, and stimulating T cell anti-tumor activity. Herein, we provide an overview of current scenario of CAR-Ms in several solid tumors, also focusing on the biological rationale behind this promising therapeutic approach and future research directions in this setting.
Insights
Chimeric antigen receptor (CAR) T cell therapy shows promise in blood cancers but struggles in solid tumors. CAR-macrophages (CAR-Ms) offer a new approach, enhancing anti-tumor activity and overcoming TME challenges.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T cell therapy is effective against hematological malignancies.
- CAR T cells face challenges in solid tumors, including poor infiltration and survival within the tumor microenvironment (TME).
- Alternative immune cells are being explored as CAR platforms to overcome these limitations.
Purpose of the Study:
- To provide an overview of CAR-macrophages (CAR-Ms) in solid tumors.
- To discuss the biological rationale for using CAR-Ms.
- To highlight future research directions for CAR-M therapy.
Main Methods:
- Review of preclinical studies on CAR-macrophages.
- Analysis of CAR expression in macrophages.
- Examination of macrophage functions like phagocytosis and phenotype polarization.
Main Results:
- CAR expression in macrophages enhances phagocytosis.
- CAR-Ms can polarize the M2 to M1 phenotype.
- CAR-Ms stimulate T cell anti-tumor activity.
Conclusions:
- CAR-macrophage technology presents a novel therapeutic strategy for solid tumors.
- CAR-Ms show potential to overcome TME-related challenges.
- Further research is needed to advance CAR-M therapy for cancer patients.
