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Review
. 2023 Feb;11(2):e005968.
doi: 10.1136/jitc-2022-005968.

Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

Iva Truxova  1 , David Cibula  2 , Radek Spisek  1   3 , Jitka Fucikova  4   3
Affiliations
Review

Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

Iva Truxova et al. J Immunother Cancer. 2023 Feb.

Abstract

Epithelial ovarian cancer (EOC) is among the top five causes of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant cells to the peritoneum. Despite improvements in medical therapies, particularly with the implementation of novel drugs targeting homologous recombination deficiency, the survival rates of patients with EOC remain low. Unlike other neoplasms, EOC remains relatively insensitive to immune checkpoint inhibitors, which is correlated with a tumor microenvironment (TME) characterized by poor infiltration by immune cells and active immunosuppression dominated by immune components with tumor-promoting properties, especially tumor-associated macrophages (TAMs). In recent years, TAMs have attracted interest as potential therapeutic targets by seeking to reverse the immunosuppression in the TME and enhance the clinical efficacy of immunotherapy. Here, we review the key biological features of TAMs that affect tumor progression and their relevance as potential targets for treating EOC. We especially focus on the therapies that might modulate the recruitment, polarization, survival, and functional properties of TAMs in the TME of EOC that can be harnessed to develop superior combinatorial regimens with immunotherapy for the clinical care of patients with EOC.

Keywords: Immunomodulation; Immunotherapy; Macrophages; Tumor Biomarkers; Tumor Microenvironment.

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Conflict of interest statement

Competing interests: RS is minority shareholder of Sotio Biotech a.s. JF and IT are employees of Sotio Biotech.

Figures

Figure 1
Figure 1
Roles of TAMs in the TME of EOC. Ovarian TME drives the polarization of TAMs predominantly toward M2-like phenotype. M2-like TAMs display limited tumoricidal activity and promote immunosuppression, tumor cell invasion and metastasis, and angiogenesis, by producing a variety of cytokines, chemokines, growth factors and other molecules. APC, antigen-presenting cell; ARG1, arginase 1; CCL, chemokine (C-C motif) ligand; EGF, epidermal growth factor; EOC, epithelial ovarian carcinoma; GATA3, GATA binding protein 3; IDO, indoleamine 2,3-dioxygenase; IL, interleukin; MDSC, myeloid-derived suppressor cell; MIP-1β, macrophage inflammatory protein 1β; miRNA, microRNA; MMP, matrix metalloproteinase; PD-L1, programmed death-ligand 1; SR-A, scavenger receptor A; TAM, tumor-associated macrophage; TGF-β, transforming growth factor β; TME, tumor microenvironment; TNF-α, tumor necrosis factor α; Treg, regulatory T cell; TREM2, triggering receptor expressed on myeloid cells 2.
Figure 2
Figure 2
TAM targets for anticancer therapy. Schematic representation of the most intensively investigated TAM-targeting strategies in EOC. Ang2, angiopoietin-2; CAR, chimeric antigen receptor; CCL2, chemokine (C-C motif) ligand 2; CCR2, chemokine (C-C motif) receptor 2; CSF1, colony-stimulating factor 1; CSF1R, colony-stimulating factor one receptor; CXCL12, C-X-C motif chemokine ligand 10; EOC, epithelial ovarian carcinoma; FRβ, folate receptor β; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon γ; IFN-γR, interferon γ receptor; IL-12, interleukin 12; IL-12R, interleukin 12 receptor; mAb, monoclonal antibody; PD-1, programmed cell death 1; PD-L1, programmed death-ligand 1; PI3K, phosphatidylinositol 3-kinase; SIGLEC10, sialic acid-binding Ig-like lectin 10; SIRPα, signal regulatory protein α; TAM, tumor-associated macrophage; TLR, toll-like receptor; TREM2, triggering receptor expressed on myeloid cells 2; VEGF, vascular endothelial growth factor
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