Bae Hee Joon, Liu Shutong, Jin Ping, Stroncek David
Cell Processing Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, U.S.A.
Emerg Top Life Sci. 2017 Dec 12;1(5):487-492. doi: 10.1042/ETLS20170141.
Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are a multipotent, heterogeneous population of cells that play a critical role in wound healing and tissue regeneration. MSCs, found in the tumor microenvironment, support tumor growth through the production of angiogenic factors, growth factors and extracellular matrix proteins. They also have immunomodulatory properties, and since they produce indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2) and transforming growth factor β (TGF-β), they have been thought to have primarily immunosuppressive effects. However, their role in the tumor microenvironment is complex and demonstrates plasticity depending on location, stimulatory factors and environment. The presence of melanoma-activated tumor-infiltrating lymphocytes (TILs) has been shown to produce pro-inflammatory changes with TH1 (type 1T helper)-like phenotype in MSCs via activated-TIL released cytokines such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin-1α (IL-1α), while simultaneously producing factors, such as IDO1, which have been traditionally associated with immunosuppression. Similarly, the combination of IFN-γ and TNF-α polarizes MSCs to a primarily TH1-like phenotype with the expression of immunosuppressive factors. Ultimately, further studies are encouraged and needed for a greater understanding of the role of MSCs in the tumor microenvironment and to improve cancer immunotherapy.
间充质干细胞（MSCs）是一类多能的异质性细胞群体，在伤口愈合和组织再生中发挥着关键作用。存在于肿瘤微环境中的MSCs通过产生血管生成因子、生长因子和细胞外基质蛋白来支持肿瘤生长。它们还具有免疫调节特性，由于能产生吲哚胺2,3-双加氧酶（IDO）、前列腺素E2（PGE2）和转化生长因子β（TGF-β），人们一直认为它们主要具有免疫抑制作用。然而，它们在肿瘤微环境中的作用是复杂的，并且根据位置、刺激因子和环境表现出可塑性。黑色素瘤激活的肿瘤浸润淋巴细胞（TILs）的存在已被证明可通过激活的TIL释放的细胞因子如干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）和白细胞介素-1α（IL-1α），使MSCs产生具有TH1（1型辅助性T细胞）样表型的促炎变化，同时产生如IDO1等传统上与免疫抑制相关的因子。同样，IFN-γ和TNF-α的组合使MSCs极化至主要具有TH1样表型并伴有免疫抑制因子的表达。最终，鼓励并需要进一步研究以更深入了解MSCs在肿瘤微环境中的作用并改善癌症免疫治疗。
