Blocking ovarian cancer progression by targeting tumor microenvironmental leukocytes.
Current therapies for metastatic ovarian carcinoma are based on surgical debulking followed by chemotherapy. After more than three decades implementing treatments that selectively target the tumor cell, the 5-year survival rate for metastatic ovarian cancer patients is still lower than 30%. Novel strategies are therefore urgently needed to complement classical treatments for this malignancy. Recently, leukocytes in the ovarian cancer microenvironment such as regulatory T cells and immature pro-angiogenic/tolerogenic myeloid cells have been demonstrated to play a fundamental role in tumor progression. This review focuses on our recent understanding of the potential of eliminating and/or modulating the phenotype of these leukocytes in vivo and in situ as a novel intervention to complement standard ovarian cancer treatments. The significant effects of targeting these crucial microenvironmental players on cancer vascularization, local tumor growth, distal metastatic spreading and spontaneous anti-tumor immune responses are discussed.
Cubillos-Ruiz
Juan R
JR
Departments of Microbiology and Immunology, Lebanon, NH, USA.
Rutkowski
Melanie
M
Conejo-Garcia
Jose R
JR
D001119:Arginase / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology* / Q000556:secondary / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D001119:Arginase