Journal article
Tumor-Associated Macrophages and Ovarian Cancer: Implications for Therapy
Cancers, Vol.14(9), 2220
04/29/2022
DOI: 10.3390/cancers14092220
PMCID: PMC9101750
PMID: 35565348
Abstract
Simple Summary Ovarian cancer is a highly lethal female malignancy with high rates of advanced stage and recurrent disease. Ovarian cancer is characterized as poorly responsive to immunotherapy. This is hypothesized to be secondary to its highly immunosuppressive and phenotypically "cold" tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are an integral component of the ovarian cancer TME, and predominantly display an M2 protumor phenotype. Ovarian cancer cells and TAMs interact via a complex network of signaling cytokines. Ovarian cancer TAMs are linked to tumor metastasis, angiogenesis, chemoresistance, and poor prognosis. Due to their profound role, TAMs represent a therapeutic target for ovarian cancer immunotherapy. Strategies for targeting TAMs include increasing phagocytosis, decreasing recruitment, decreasing macrophage survival, and repolarizing TAMs to an antitumor phenotype. The tumor microenvironment (TME) has been implicated to play an important role in the progression of ovarian cancer. One of the most important components of the TME is tumor associated macrophages (TAMs). Phenotypically, macrophages are broadly categorized as M1 pro-inflammatory or M2 anti-inflammatory, based on the cytokines and chemokines that they secrete. The tumor microenvironment is associated with macrophages of an M2 phenotype which suppress the surrounding immune environment, assist tumor cells in evading immune targeting, and support tumor growth and metastasis. Contrarily, M1 macrophages help mount an immune response against tumors, and are associated with a more favorable prognosis in solid tumors. One of the characteristic indicators of a poor prognosis in ovarian cancer is the overrepresentation of M2-type TAMs. As such, therapeutic modalities targeting TME and TAMs are of increasing interest. Pharmacological approaches to eliminate TAMs, include decreasing macrophage survival and recruitment and increasing phagocytosis, have been underwhelming. Clinical strategies targeting these macrophage subtypes via repolarization to an M1 antitumoral state deserve increasing attention, and may serve as a new modality for immunotherapy.
Details
- Title: Subtitle
- Tumor-Associated Macrophages and Ovarian Cancer: Implications for Therapy
- Creators
- David Schweer - Markey Cancer CenterAnnabel McAtee - University of KentuckyKhaga Neupane - University of KentuckyChristopher Richards - University of KentuckyFrederick Ueland - University of KentuckyJill Kolesar - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.14(9), 2220
- Publisher
- Mdpi
- DOI
- 10.3390/cancers14092220
- PMID
- 35565348
- PMCID
- PMC9101750
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Number of pages
- 18
- Grant note
- P30 CA177558 / University of Kentucky Markey Cancer Center T32CA160003 / NIH Training Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 04/29/2022
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696550302771
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