Year: 2018
Type: article
Abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of innate immune cells that play critical roles in cancer [1].MDSCs can be categorized into two populations that resemble immature forms of either monocytes or neutrophils.MDSCs are differentiated from their cellular relatives by unique functional characteristics.Namely, MDSCs suppress T cell activation and effector T cell functions.During cancer progression, MDSCs are mobilized from the bone marrow to infiltrate tumors and immune foci leading to the development of immunosuppressive microenvironments.Multifocal suppression leads to reduced efficacy of immunotherapies, like checkpoint inhibitors and cell therapies, that rely upon an active adaptive immune response to clear cancer [2].Agents that inhibit MDSCs may prevent cancer, reduce metastasis, and increase the efficacy of therapies aimed at harnessing adaptive immunity to eradicate advanced disease.There is tremendous interest in identifying factors that control MDSCs.But first, the role of cholesterol in myeloid cells deserves attention.In 2010, Yvan-Charvet et al discovered that knocking out ATP-binding cassette transporters, ABCA1 and ABCG1, increased proliferation of myeloid cells [3].ABCA1 and ABCG1 are responsible for effluxing cellular cholesterol to apolipoprotein A-I (apoA-I) containing high-density lipoproteins (HDL).ApoA-I is the main protein constituent of HDLs.Cholesterol efflux to HDLs, particularly through ABCA1, promotes the formation of "mature", cholesterolrich, spherical HDLs that can deliver their payload of cholesterol to cells by binding scavenger receptor type B1 (SR-B1).Yvan-Charvet et al reported that administration of exogenous HDL to mice lacking ABCA1 and ABCG1 reduced the myeloproliferative phenotype to baseline suggesting that HDLs suppress myeloid cell proliferation independently of these receptors.These data implicate other receptors for HDL, particularly SR-B1, in the control of myeloid proliferation.At the time, connections between HDL, cholesterol, and myeloid cells during cancer progression were not fully appreciated.Studies began to link these concepts as Zamanian-Daryoush et al demonstrated in mouse models of cancer that mice lacking apoA-I had increased tumor growth and metastasis [4].Additionally, high-dose infusion of apoA-I reduced metastasis and tumor burden.Although,
Source: Oncoscience
Institution: Northwestern University
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2980824660