Targeting Tumor-Associated Macrophages to Synergize Tumor Immunotherapy

Scientists summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition, tumor vaccines and adoptive cell transfer therapies.
[Signal Transduction and Targeted Therapy]
Xiang, X., Wang, J., Lu, D., & Xu, X. (2021). Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduction and Targeted Therapy, 6(1), 1–12. https://doi.org/10.1038/s41392-021-00484-9 Cite
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Complement Activation Promoted by the Lectin Pathway Mediates C3aR-Dependent Sarcoma Progression and Immunosuppression

Scientists conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. Mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects.
[Nature Cancer]
Magrini, E., Di Marco, S., Mapelli, S. N., Perucchini, C., Pasqualini, F., Donato, A., Guevara Lopez, M. de la L., Carriero, R., Ponzetta, A., Colombo, P., Cananzi, F., Supino, D., Reis, E. S., Peano, C., Inforzato, A., Jaillon, S., Doni, A., Lambris, J. D., Mantovani, A., & Garlanda, C. (2021). Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression. Nature Cancer, 2(2), 218–232. https://doi.org/10.1038/s43018-021-00173-0 Cite
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Imbalance of TGF-β1/BMP-7 Pathways Induced by M2-polarized Macrophages Promotes Hepatocellular Carcinoma Aggressiveness

Investigators found that the imbalance of TGF-β1/BMP-7 pathways was associated with aggressive pathological features and poor clinical outcomes in hepatocellular carcinoma.
[Molecular Therapy]
Ning, J., Ye, Y., Bu, D., Zhao, G., Song, T., Liu, P., Yu, W., Wang, H., Li, H., Ren, X., Ying, G., Zhao, Y., & Yu, J. (2021). Imbalance of TGF-β1/BMP-7 Pathways Induced by M2-polarized Macrophages Promotes Hepatocellular Carcinoma Aggressiveness. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.02.016 Cite
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Macrophages Support the Aggressive Mechanical Phenotype of Circulating Tumor Cells in Prostate Cancer

Investigators recapitulated the tumor cells – macrophages interactions in cell culture using prostate cancer cell lines.
[Biophysical Journal]
Osmulski, P. A., Cunsolo, A., Qian, Y., Chen, M., Lin, C.-L., Hung, C.-N., Mahalingam, D., Kirma, N., Chen, C.-L., Taverna, J., Liss, M., Thompson, I. M., Huang, T. H., & Gaczynska, M. (2021). Macrophages Support the Aggressive Mechanical Phenotype of Circulating Tumor Cells in Prostate Cancer. Biophysical Journal, 120(3), 64a–65a. https://doi.org/10.1016/j.bpj.2020.11.619 Cite
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Tumor-Derived Exosomal MicroRNA-106b-5p Activates the Interaction between EMT-Cancer Cells and M2-Subtype TAMs to Facilitate Colorectal Cancer Metastasis

Scientists found that epithelial-mesenchymal transition (EMT)-colorectal cancer cells promoted the M2-like polarization of macrophages by directly transferring exosomes to macrophages, leading to a significant increase of miR-106b level in macrophages.
[Molecular Therapy]
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CAR-T Cell-Mediated Depletion of Immunosuppressive Tumor-Associated Macrophages Promotes Endogenous Antitumor Immunity and Augments Adoptive Immunotherapy

Researchers demonstrated that a subset of tumor-associated macrophages that express folate receptor β possessed an immunosuppressive M2-like profile.
[Nature Communications]
Rodriguez-Garcia, A., Lynn, R. C., Poussin, M., Eiva, M. A., Shaw, L. C., O’Connor, R. S., Minutolo, N. G., Casado-Medrano, V., Lopez, G., Matsuyama, T., & Powell, D. J. (2021). CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nature Communications, 12(1), 877. https://doi.org/10.1038/s41467-021-20893-2 Cite
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HDAC Inhibition Potentiates Anti-tumor Activity of Macrophages and Enhances Anti-PD-L1-Mediated Tumor Suppression

Scientists demonstrated that low-dose HDAC inhibitor trichostatin-A markedly reshaped the tumor immune microenvironment by modulating the suppressive activity of infiltrating macrophages and inhibiting the recruitment of myeloid-derived suppressor cells in various tumors.
[Oncogene]
Li, X., Su, X., Liu, R., Pan, Y., Fang, J., Cao, L., Feng, C., Shang, Q., Chen, Y., Shao, C., & Shi, Y. (2021). HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01636-x Cite
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ECT2 Overexpression Promotes the Polarization of Tumor-Associated Macrophages in Hepatocellular Carcinoma via the ECT2/PLK1/PTEN Pathway

In vitro experiments were used to investigate the underlying mechanism and function of epithelial cell transforming 2 (ECT2), and the results were confirmed through in vivo experiments.
[Cell Death & Disease]
Xu, D., Wang, Y., Wu, J., Zhang, Z., Chen, J., Xie, M., Tang, R., Chen, C., Chen, L., Lin, S., Luo, X., & Zheng, J. (2021). ECT2 overexpression promotes the polarization of tumor-associated macrophages in hepatocellular carcinoma via the ECT2/PLK1/PTEN pathway. Cell Death & Disease, 12(2), 1–15. https://doi.org/10.1038/s41419-021-03450-z Cite
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Cyclodextrin-Based Host-Guest Complexes Loaded with Regorafenib for Colorectal Cancer Treatment

In vivo application showed that a channel-type formulation optimized the pharmacokinetics and bio-distribution of Regorafenib (Rg). In colitis-associated cancer and CT26 mouse models, RG mannose-modified γ-cyclodextrin was proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels tumor microenvironment.
[Nature Communications]
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Nod1 Promotes Colorectal Carcinogenesis by Regulating the Immunosuppressive Functions of Tumor-Infiltrating Myeloid Cells

Scientists demonstrated the immunosuppressive potential of Nod1, the bacterial sensor of diaminopimelic acid-containing muramyl peptides.
[Cell Reports]
Maisonneuve, C., Tsang, D. K. L., Foerster, E. G., Robert, L. M., Mukherjee, T., Prescott, D., Tattoli, I., Lemire, P., Winer, D. A., Winer, S., Streutker, C. J., Geddes, K., Cadwell, K., Ferrero, R. L., Martin, A., Girardin, S. E., & Philpott, D. J. (2021). Nod1 promotes colorectal carcinogenesis by regulating the immunosuppressive functions of tumor-infiltrating myeloid cells. Cell Reports, 34(4). https://doi.org/10.1016/j.celrep.2020.108677 Cite
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Tumor-Associated Myeloid Cells: Diversity and Therapeutic Targeting

Scientists provide an overview of the recent literature on the ever-growing complexity of the biology of tumor-associated macrophages and tumor-associated neutrophils and the development of the most promising approaches to target these populations therapeutically in cancer patients.
[Cellular & Molecular Immunology]
Mantovani, A., Marchesi, F., Jaillon, S., Garlanda, C., & Allavena, P. (2021). Tumor-associated myeloid cells: diversity and therapeutic targeting. Cellular & Molecular Immunology, 1–13. https://doi.org/10.1038/s41423-020-00613-4 Cite
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