The Role of Tumor-Associated Macrophages (TAMs) in Cancer Progression and Immunosuppression
The Role of TAMs in Cancer progression
DOI:
https://doi.org/10.29409/sz9tyq96Keywords:
CD163, gene expression, immunosuppression, microenvironment, macrophages, PD-L1, solid tumorsAbstract
Tumor-associated macrophages (TAMs) are important immunological components that influence the tumor microenvironment by inhibiting immune responses and encouraging tumor development and cellular proliferation. This study sought to assess the functional, morphological, and molecular functions of TAMs in solid tumor patients. This study used a number of methods, such as flow cytometry, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. Blood samples were taken from 50 patients clinically diagnosed with solid tumors, as well as from 30 healthy individuals who served as controls. Cytological investigations revealed a considerable increase in the percentage of macrophages bearing the CD163 and CD204 markers, as well as a decrease in HLA-DR expression, indicating that the cells polarized toward the M2 immunophenotype with immunosuppressive features. Additional genetic analyses revealed elevated expression of IL-10, TGF-β, ARG1, CSF-1R, and MMP9, genes linked to the immunosuppressive tumor microenvironment (TME). Histological evaluations revealed distinct infiltration of macrophages toward tumor peripheral zones and increased PD-L1 expression by macrophages, suggesting that macrophages may participate in the regulation of immunological checkpoints in addition to the suppression of effector T lymphocytes. Statistical analyses showed an inverse correlation between PD-L1 and HLA-DR and a positive correlation with IL-10, supporting the notion of the pleiotropic immunosuppressive function of macrophages. These data underscore the importance of TAMs for tumor progression and suppression, thereby rendering them suitable targets for contemporary immunotherapeutic approaches. Research suggests that additional investigations on the potential for reprogramming or targeting these cells therapeutically to enhance the immunotherapy response in solid tumors are needed.
References
1. Qiyao Yang, Ningning Guo, Yi Zhou, Jiejian Chen, Qichun Wei, Min Han,The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy,Acta Pharmaceutica Sinica ,2020,Pages 2156-2170,
2. Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Research. 2021;81(2):401–405. doi:10.1158/0008-5472.CAN-20-1234
3. Movahedi K, Laoui D, Gysemans C, Baeten M, Stangé G, Van den Bossche J, et al. Macrophage infiltration into tumors: modulation by tumor-derived signals. Frontiers in Oncology. 2022;12:880223. doi:10.3389/fonc.2022.880223
4. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumor-associated macrophages as treatment targets in oncology. Nature Reviews Clinical Oncology. 2017;14(7):399–416. doi:10.1038/nrclinonc.2016.217
5. Locati M, Curtale G, Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annual Review of Pathology: Mechanisms of Disease. 2020;15:123–147. doi:10.1146/annurev-pathmechdis-012418-012718
6. Chen Y, Song Y, Du W, Gong L, Chang H, Zou Z. Tumor-associated macrophages: an accomplice in solid tumor progression. Journal of Biomedical Science. 2019;26(1):78. doi:10.1186/s12929-019-0568-z
7. Zeng Q, et al. Targeting TAMs to overcome the immunosuppressive TME in cancer therapy. Frontiers in Immunology. 2021;12:684397.
8. Poh AR, Ernst M. Targeting macrophages in cancer: from bench to bedside. Frontiers in Oncology. 2021;11:788365.
9. Cassetta L, Pollard JW. Tumor-associated macrophages. Current Biology. 2020;30(6):R246–R248.
10. Zhang QW, et al. High tumor-associated macrophage infiltration and poor prognosis in human hepatocellular carcinoma. Cancer Letters. 2020;482:194–202.
11. Xuan W, et al. Tumor-associated macrophages in tumor metastasis: biological roles and potential therapeutic targets. Signal Transduction and Targeted Therapy. 2021;6(1):1–16.
12. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2021;141(1):39–51. doi:10.1016/j.cell.2021.01.011
13. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, et al. Targeting tumor‐associated macrophages with anti-CSF-1R antibody in cancer therapy. Cancer Cell. 2014;25(6):846–859. doi:10.1016/j.ccr.2014.05.016
14. Salvagno C, Ciampricotti M, Tuit S, Hau C-S, van Weverwijk A, Coffelt SB, et al. Immunosuppressive tumor-associated macrophages: barriers to antitumor immunity. Oncoimmunology. 2022;11(1):e2017291. doi:10.1080/2162402X.2022.2017291
15. Hoves S, Cannarile MA, Ries CH, Höfle L, Kelderman S, van der Vijn P, et al. TAM reprogramming enhances tumor immunity. Journal of Experimental Medicine. 2022;219(3):e20211940. doi:10.1084/jem.20211940
16. Makkouk A, Weiner GJ. Cancer immunotherapy and breaking immune tolerance: new approaches to activate macrophages against tumors. Frontiers in Immunology.2020;11:588857. doi:10.3389/fimmu.2020.588857
17. Liu Y, Li X, Zhang B, Wang C, Zhao L, Chen Y, et al. Reprogramming TAMs to overcome resistance to immune checkpoint blockade. Cancer Discovery. 2024;14(1):56–70. doi:10.1158/2159-8290.CD-23-0987
18. Al-Ukaily HAM, Alqaisi AAS, Ali HM, Kashkul SA, Rasheed WJ, Abood AJ. Cytotoxic T Lymphocytes’ Function in an Adenovirus Infection. American Journal of Biology and Natural Sciences. 2025;2(4):81–91. doi:10.51699/ajbns.v2i4.887
19. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nature Medicine. 2013;19(11):1423–1437. doi:10.1038/nm.3394
20. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
21. Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019 Dec;25(12):1822-32.
22. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7.
23. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010 Mar 19;140(6):883-99.
24. DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol. 2019 Jun;19(6):369-82.
25. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014 Jul 17;41(1):49-61.
26. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013 Oct;14(10):1014-22.
27. Gordon S, Martinez FO. Alternative activation of macrophages: mechanism and functions. Immunity. 2010 May 28;32(5):593-604.
28. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011 Nov;11(11):723-37.
29. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018 Sep;233(9):6425-40.
30. Mantovani, A., & Allavena, P. (2015). Tumor-associated macrophages and the inflammatory microenvironment of tumors. Current Opinion in Immunology, 34, 26–32. https://doi.org/10.1016/j.coi.2015.02.002
31. Noy, R., & Pollard, J. W. (2014). Tumor-associated macrophages: From mechanisms to therapy. Immunity, 41(1), 49–61. https://doi.org/10.1016/j.immuni.2014.09.008.
32. Murray, P. J., Allen, J. E., Biswas, S. K., Fisher, E. A., Gilroy, D. W., Goerdt, S., Gordon, S., Hamilton, J. A., Ivashkiv, L. B., Lawrence, T., Locati, M., Mantovani, A., Martinez, F. O., Mege, J. L., Mosser, D. M., Natoli, G., Saeij, J. P., Schultze, J. L., Shirey, K. A., … Wynn, T. A. (2014). Macrophage activation and polarization: Nomenclature and experimental guidelines. Immunity, 41(1), 14–20. https://doi.org/10.1016/j.immuni.2014.06.008
33. Qian, B. Z., & Pollard, J. W. (2010). Macrophage diversity enhances tumor progression and metastasis. Cell, 141(1), 39–51. https://doi.org/10.1016/j.cell.2010.03.021
34. Chen, D. S., & Mellman, I. (2013). Oncology meets immunology: The cancer–immunity cycle. Immunity, 39(1), 1–10. https://doi.org/10.1016/j.immuni.2013.07.012
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Data Availability Statement
The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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