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Review
. 2021 Oct;9(10):e002873.
doi: 10.1136/jitc-2021-002873.

Immunological configuration of ovarian carcinoma: features and impact on disease outcome

Jitka Fucikova  1   2 , An Coosemans  3 , Sandra Orsulic  4 , David Cibula  5 , Ignace Vergote  6 , Lorenzo Galluzzi  7   8   9 , Radek Spisek  10   2
Affiliations
Review

Immunological configuration of ovarian carcinoma: features and impact on disease outcome

Jitka Fucikova et al. J Immunother Cancer. 2021 Oct.

Abstract

Epithelial ovarian carcinoma (EOC) is a relatively rare malignancy but is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. At odds with other neoplasms, EOC is virtually insensitive to immune checkpoint inhibitors, correlating with a tumor microenvironment that exhibits poor infiltration by immune cells and active immunosuppression. Here, we comparatively summarize the humoral and cellular features of primary and metastatic EOC, comparatively analyze their impact on disease outcome, and propose measures to alter them in support of treatment sensitivity and superior patient survival.

Keywords: female; genital neoplasms; immunologic surveillance; immunotherapy; tumor biomarkers; tumor microenvironment.

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Conflict of interest statement

Competing interests: JF and RS are employees of Sotio Biotech a.s.; IV declares consulting for Astra Zeneca, Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, F. Hoggmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Octimet Oncology NV, Oncoinvent AS, Sotio a.s., Verastem Oncology, Zentalis; contracted research for Oncoinvent AS, Genmab; research funding from Amgen, Roche; LG declares research funding from Lytix and Phosplatin (completed) and speaker and/or advisory honoraria from Boehringer Ingelheim, Astra Zeneca, OmniSEQ, The Longevity Labs, Inzen, Onxeo, the Luke Heller TECPR2 Foundation; SO has patents for molecular signatures in ovarian cancer (US10253368 and EU2908913) and is funded by NCI (R01 CA208753) and VA (VA-ORD BX004974) grants. AC declares consulting for SOTIO; contracted research for Novocure and Oncoinvent.

Figures

Figure 1
Figure 1
Principle of cancer immunosurveillance in primary and metastatic ovarian carcinoma. Primary immune cell populations, cytokines and chemokines involved in the interaction between primary and metastatic ovarian carcinoma and the host immune system. ARG1, arginase 1; CCL, chemokine (C-C motif) ligand; CXCL, chemokine (C-X-C motif) ligand; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; GITR, glucocorticoid-induced TNFR related gene; GZMB, granzyme B; IDO1, indoleamine 2,3-dioxygenase 1; IFNG, interferon gamma; IL, interleukin; LAG3, lymphocyte activation gene 3; mDCs, myeloid dendritic cells; MDSCs, myeloid-derived suppressor cells; NK, natural killer; PD-1, programmed cell death 1; PD–L1, programmed death ligand 1; pDC, plasmacytoid dendritic cell; PGE2, prostaglandin E2; PRF1, perforin 1; TAM, tumor-associated macrophage; TIM-3, coinhibitory receptor hepatitis A virus cellular receptor 2 (HAVCR2, best known as Tim-3); TGFB1, transforming growth factor beta 1; TLS, tertiary lymphoid structure; TNF, tumor necrosis factor; TREG, regulatory T cell; VEGFA, vascular endothelial growth factor A.
Figure 2
Figure 2
Cytokines and chemokines that coordinate the tumor microenvironment. Primary cytokines (A) and chemokines (B) produced in the ovarian tumor microenvironment. The most prominent sources and major receptors are depicted. CCL, chemokine (C-C motif) ligand; CCR, C-C chemokine receptor; CXCL, chemokine (C-X-C motif) ligand; CXCR, C-X-C chemokine receptor; CTL, cytotoxic T lymphocyte; IL, interleukin; IL6R, interleukin 6 receptor; MDSC, myeloid-derived suppressor cell; NK, natural killer; pDC, plasmacytoid dendritic cell; TAM, tumor-associated macrophage; TGFB1, transforming growth factor beta 1; TGFBR, transforming growth factor beta receptor; TNF, tumor necrosis factor; TNFR, tumor necrosis factor receptor; TREG, regulatory T; VEGFA, vascular endothelial growth factor A; VEGFR, vascular endothelial growth factor receptor.
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