Targeting Macrophages in Cancer Immunotherapy

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2021 Mar 26

PMID 33767177

Citations 252

Authors

Zhaojun Duan

Yunping Luo

Affiliations

Soon will be listed here.

Abstract

Immunotherapy is regarded as the most promising treatment for cancers. Various cancer immunotherapies, including adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small-molecule inhibitors, have achieved certain successes. In this review, we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages. To better understand and make better use of this type of cell, their development and differentiation characteristics, categories, typical markers, and functions were collated at the beginning of the review. Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

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References

Franklin R, Liao W, Sarkar A, Kim M, Bivona M, Liu K . The cellular and molecular origin of tumor-associated macrophages. Science. 2014; 344(6186):921-5. PMC: 4204732. DOI: 10.1126/science.1252510. View

Fu J, Kanne D, Leong M, Glickman L, McWhirter S, Lemmens E . STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci Transl Med. 2015; 7(283):283ra52. PMC: 4504692. DOI: 10.1126/scitranslmed.aaa4306. View

Velmurugan R, Challa D, Ram S, Ober R, Ward E . Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells. Mol Cancer Ther. 2016; 15(8):1879-89. PMC: 4975628. DOI: 10.1158/1535-7163.MCT-15-0335. View

A-Gonzalez N, Castrillo A . Origin and specialization of splenic macrophages. Cell Immunol. 2018; 330:151-158. DOI: 10.1016/j.cellimm.2018.05.005. View

Liu Y, Cao X . The origin and function of tumor-associated macrophages. Cell Mol Immunol. 2014; 12(1):1-4. PMC: 4654376. DOI: 10.1038/cmi.2014.83. View

Varol C, Yona S, Jung S . Origins and tissue-context-dependent fates of blood monocytes. Immunol Cell Biol. 2008; 87(1):30-8. DOI: 10.1038/icb.2008.90. View

Hashimoto D, Miller J, Merad M . Dendritic cell and macrophage heterogeneity in vivo. Immunity. 2011; 35(3):323-35. PMC: 4520532. DOI: 10.1016/j.immuni.2011.09.007. View

Okamoto A, Nikaido T, Ochiai K, Takakura S, Saito M, Aoki Y . Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells. Clin Cancer Res. 2005; 11(16):6030-9. DOI: 10.1158/1078-0432.CCR-04-2671. View

Kong Y, Yoshida H, Sarosi I, Tan H, Timms E, Capparelli C . OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999; 397(6717):315-23. DOI: 10.1038/16852. View

10.

Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K . Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A. 1993; 90(8):3539-43. PMC: 46336. DOI: 10.1073/pnas.90.8.3539. View

11.

Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A . Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011; 19(4):512-26. DOI: 10.1016/j.ccr.2011.02.005. View

12.

Beatty G, Chiorean E, Fishman M, Saboury B, Teitelbaum U, Sun W . CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011; 331(6024):1612-6. PMC: 3406187. DOI: 10.1126/science.1198443. View

13.

Hanayama R, Tanaka M, Miyasaka K, Aozasa K, Koike M, Uchiyama Y . Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice. Science. 2004; 304(5674):1147-50. DOI: 10.1126/science.1094359. View

14.

Klein I, Cornejo J, Polakos N, John B, Wuensch S, Topham D . Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood. 2007; 110(12):4077-85. PMC: 2190614. DOI: 10.1182/blood-2007-02-073841. View

15.

Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C . Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012; 18(8):1254-61. DOI: 10.1038/nm.2883. View

16.

Hulsmans M, Clauss S, Xiao L, Aguirre A, King K, Hanley A . Macrophages Facilitate Electrical Conduction in the Heart. Cell. 2017; 169(3):510-522.e20. PMC: 5474950. DOI: 10.1016/j.cell.2017.03.050. View

17.

Hashimoto D, Chow A, Noizat C, Teo P, Beasley M, Leboeuf M . Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity. 2013; 38(4):792-804. PMC: 3853406. DOI: 10.1016/j.immuni.2013.04.004. View

18.

Chiocca E, Rabkin S . Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res. 2014; 2(4):295-300. PMC: 4303349. DOI: 10.1158/2326-6066.CIR-14-0015. View

19.

Gordon S, Maute R, Dulken B, Hutter G, George B, McCracken M . PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature. 2017; 545(7655):495-499. PMC: 5931375. DOI: 10.1038/nature22396. View

20.

Zhu X, Shen H, Yin X, Yang M, Wei H, Chen Q . Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res. 2019; 38(1):81. PMC: 6377760. DOI: 10.1186/s13046-019-1095-1. View