Heme Catabolism by Tumor-Associated Macrophages Controls Metastasis Formation

Scientists showed that a distinct subset of tumor-associated macrophages, endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1, played a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition.
[Nature Immunology]
Consonni, F. M., Bleve, A., Totaro, M. G., Storto, M., Kunderfranco, P., Termanini, A., Pasqualini, F., Alì, C., Pandolfo, C., Sgambelluri, F., Grazia, G., Santinami, M., Maurichi, A., Milione, M., Erreni, M., Doni, A., Fabbri, M., Gribaldo, L., Rulli, E., … Sica, A. (2021). Heme catabolism by tumor-associated macrophages controls metastasis formation. Nature Immunology, 1–12. https://doi.org/10.1038/s41590-021-00921-5 Cite
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CD169+ Lymph Node Macrophages Have Protective Functions in Mouse Breast Cancer Metastasis

Researchers found CD169+ macrophages as the predominant macrophage subtype in naive lymph nodes, which underwent proliferative expansion in response to tumor stimuli.
[Cell Reports]
Tacconi, C., Commerford, C. D., Dieterich, L. C., Schwager, S., He, Y., Ikenberg, K., Friebel, E., Becher, B., Tugues, S., & Detmar, M. (2021). CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis. Cell Reports, 35(2). https://doi.org/10.1016/j.celrep.2021.108993 Cite
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Glioblastomas Acquire Myeloid-Affiliated Transcriptional Programs via Epigenetic Immunoediting to Elicit Immune Evasion

By serially transplanting glioblastoma multiforme stem cells (GSCs) into immunocompetent hosts, scientists uncovered an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment.
[Cell]
Gangoso, E., Southgate, B., Bradley, L., Rus, S., Galvez-Cancino, F., McGivern, N., Güç, E., Kapourani, C.-A., Byron, A., Ferguson, K. M., Alfazema, N., Morrison, G., Grant, V., Blin, C., Sou, I., Marques-Torrejon, M. A., Conde, L., Parrinello, S., Herrero, J., … Pollard, S. M. (2021). Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion. Cell, 0(0). https://doi.org/10.1016/j.cell.2021.03.023 Cite
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The IRENA lncRNA Converts Chemotherapy-Polarized Tumor-Suppressing Macrophages to Tumor-Promoting Phenotypes in Breast Cancer

Scientists found that IFN-activated proinflammatory macrophages after neoadjuvant chemotherapy enhanced antitumor immunity but promoted cancer chemoresistance.
[Nature Cancer]
Liu, J., Lao, L., Chen, J., Li, J., Zeng, W., Zhu, X., Li, J., Chen, X., Yang, L., Xing, Y., Chen, F., Huang, D., Zhang, X., Wei, W., Gong, C., Huang, S., Yu, Z., Li, Z., Yang, L., … Song, E. (2021). The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer. Nature Cancer, 1–17. https://doi.org/10.1038/s43018-021-00196-7 Cite
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Mutant KRAS Triggers Functional Reprogramming of Tumor-Associated Macrophages in Colorectal Cancer

Mutationally activated KRAS in tumor cells reprograms macrophages to a tumor-associated macrophage-like phenotype via a combination effect of tumor-derived CSF2 and lactate.
[Signal Transduction and Targeted Therapy]
Liu, H., Liang, Z., Zhou, C., Zeng, Z., Wang, F., Hu, T., He, X., Wu, X., Wu, X., & Lan, P. (2021). Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer. Signal Transduction and Targeted Therapy, 6(1), 1–13. https://doi.org/10.1038/s41392-021-00534-2 Cite
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How to Turn Up the Heat on the Cold Immune Microenvironment of Metastatic Prostate Cancer

The authors discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies.
[Prostate Cancer and Prostatic Diseases]
Stultz, J., & Fong, L. (2021). How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer. Prostate Cancer and Prostatic Diseases, 1–21. https://doi.org/10.1038/s41391-021-00340-5 Cite
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Hypoxic Glioma-Derived Exosomes Promote M2-Like Macrophage Polarization by Enhancing Autophagy Induction

The authors investigated the effects of glioma-derived exosomes on autophagy, the polarization of tumor-associated macrophages, and glioma progression.
[Cell Death & Disease]
Xu, J., Zhang, J., Zhang, Z., Gao, Z., Qi, Y., Qiu, W., Pan, Z., Guo, Q., Li, B., Zhao, S., Guo, X., Qian, M., Chen, Z., Wang, S., Gao, X., Zhang, S., Wang, H., Guo, X., Zhang, P., … Li, G. (2021). Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction. Cell Death & Disease, 12(4), 1–16. https://doi.org/10.1038/s41419-021-03664-1 Cite
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A Highly Selective and Potent CXCR4 Antagonist for Hepatocellular Carcinoma Treatment

A highly selective, safe, and potent CXCR4 antagonist, BPRCX807, has been designed and experimentally validated in various hepatocellular carcinoma models.
[Proceedings of the National Academy of Sciences of the United States of America]
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Single-Cell Profiling of Myeloid Cells in Glioblastoma across Species and Disease Stage Reveals Macrophage Competition and Specialization

Scientists employed single-cell RNA sequencing and CITE-seq to map the glioblastoma immune landscape in mouse tumors and in patients with newly diagnosed disease or recurrence.
[Nature Neuroscience]
Pombo Antunes, A. R., Scheyltjens, I., Lodi, F., Messiaen, J., Antoranz, A., Duerinck, J., Kancheva, D., Martens, L., De Vlaminck, K., Van Hove, H., Kjølner Hansen, S. S., Bosisio, F. M., Van der Borght, K., De Vleeschouwer, S., Sciot, R., Bouwens, L., Verfaillie, M., Vandamme, N., Vandenbroucke, R. E., … Movahedi, K. (2021). Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization. Nature Neuroscience, 1–16. https://doi.org/10.1038/s41593-020-00789-y Cite
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EZH2 Inhibition Activates a dsRNA–STING–Interferon Stress Axis That Potentiates Response to PD-1 Checkpoint Blockade in Prostate Cancer

Scientists demonstrated that enhancer of zeste homolog-2 (EZH2) inhibition in prostate cancer models activated a double-stranded RNA–STING–ISG stress response upregulating genes involved in antigen presentation, Th1 chemokine signaling and interferon response, including programmed cell death protein 1 (PD-L1) that was dependent on STING activation.
[Nature Cancer]
Morel, K. L., Sheahan, A. V., Burkhart, D. L., Baca, S. C., Boufaied, N., Liu, Y., Qiu, X., Cañadas, I., Roehle, K., Heckler, M., Calagua, C., Ye, H., Pantelidou, C., Galbo, P., Panja, S., Mitrofanova, A., Wilkinson, S., Whitlock, N. C., Trostel, S. Y., … Ellis, L. (2021). EZH2 inhibition activates a dsRNA–STING–interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer. Nature Cancer, 1–13. https://doi.org/10.1038/s43018-021-00185-w Cite
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4-Methylumbelliferone-Mediated Polarization of M1 Macrophages Correlate with Decreased Hepatocellular Carcinoma Aggressiveness in Mice

The authors observed that 4-methylumbelliferone (4Mu) therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and hepatocellular carcinoma cells exposed to conditioned medium derived from Mϕ treated with 4Mu showed reduced expression of several cancer stem cells markers and aggressiveness.
[Scientific Reports]
Rodríguez, M. M., Onorato, A., Cantero, M. J., Domínguez, L., Bayo, J., Fiore, E., García, M., Atorrasagasti, C., Canbay, A., Malvicini, M., & Mazzolini, G. D. (2021). 4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice. Scientific Reports, 11(1), 6310. https://doi.org/10.1038/s41598-021-85491-0 Cite
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