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Updated: Feb 8, 2026

Studying Interactions between Myeloid Cells and CAR T Cells In Vitro and In Vivo
Published on: July 25, 2025
Turn CAR T against TAMs
Alberto Mantovani1, Cecilia Garlanda2
1IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy; William Harvey Research Institute, Queen Mary University, London EC1M 6BQ, UK.
Abstract:
The diversity of tumor-associated macrophages presents a major challenge to the clinical translation of myeloid cell-targeting strategies. In this issue of Cancer Cell, Yagel et al. and Mateus-Tique et al. demonstrate that IL-12 armored CAR T cells effectively target tumor-promoting macrophage populations and reset the microenvironment toward an anti-cancer mode.
Insights
Interleukin-12 (IL-12) armored chimeric antigen receptor (CAR) T cells effectively target tumor-promoting macrophages. This approach resets the tumor microenvironment to combat cancer growth.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment.
- TAM diversity poses a significant challenge for myeloid cell-targeting cancer therapies.
- Current strategies face difficulties in effectively targeting pro-tumorigenic macrophage populations.
Purpose of the Study:
- To investigate the efficacy of Interleukin-12 (IL-12) armored chimeric antigen receptor (CAR) T cells.
- To determine if this approach can target and modify tumor-promoting macrophage populations.
- To assess the potential of resetting the tumor microenvironment towards an anti-cancer state.
Main Methods:
- Development of IL-12 armored CAR T cells.
- In vivo and in vitro studies utilizing specific tumor models.
- Analysis of macrophage populations and tumor microenvironment modulation.
Main Results:
- IL-12 armored CAR T cells demonstrated effective targeting of tumor-promoting macrophages.
- Successful reprogramming of the tumor microenvironment from a pro-tumor to an anti-cancer state.
- Evidence of enhanced anti-tumor activity mediated by the modified T cells.
Conclusions:
- IL-12 armored CAR T cells represent a promising strategy for targeting TAMs.
- This approach offers a novel method for modulating the tumor microenvironment.
- Potential for improved clinical translation of myeloid cell-based cancer therapies.
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