Molecular Oncology and Angiogenesis Unit, Policlinico San Martino, Genoa, Italy.
Division of Immunology, Transplants and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
Front Immunol. 2018 Feb 19;9:262. doi: 10.3389/fimmu.2018.00262. eCollection 2018.
Experimental evidence indicates that mesenchymal stromal cells (MSCs) may regulate tumor microenvironment (TME). It is conceivable that the interaction with MSC can influence neoplastic cell functional behavior, remodeling TME and generating a tumor cell niche that supports tissue neovascularization, tumor invasion and metastasization. In addition, MSC can release transforming growth factor-beta that is involved in the epithelial-mesenchymal transition of carcinoma cells; this transition is essential to give rise to aggressive tumor cells and favor cancer progression. Also, MSC can both affect the anti-tumor immune response and limit drug availability surrounding tumor cells, thus creating a sort of barrier. This mechanism, in principle, should limit tumor expansion but, on the contrary, often leads to the impairment of the immune system-mediated recognition of tumor cells. Furthermore, the cross-talk between MSC and anti-tumor lymphocytes of the innate and adaptive arms of the immune system strongly drives TME to become immunosuppressive. Indeed, MSC can trigger the generation of several types of regulatory cells which block immune response and eventually impair the elimination of tumor cells. Based on these considerations, it should be possible to favor the anti-tumor immune response acting on TME. First, we will review the molecular mechanisms involved in MSC-mediated regulation of immune response. Second, we will focus on the experimental data supporting that it is possible to convert TME from immunosuppressive to immunostimulant, specifically targeting MSC.
实验证据表明，间充质基质细胞（MSCs）可能调节肿瘤微环境（TME）。可以想象，与 MSC 的相互作用会影响肿瘤细胞的功能行为，重塑 TME 并产生支持组织新生血管生成、肿瘤侵袭和转移的肿瘤细胞龛。此外，MSC 可以释放参与癌细胞上皮间质转化的转化生长因子-β；这种转化对于产生侵袭性肿瘤细胞和促进癌症进展至关重要。此外，MSC 既能影响抗肿瘤免疫反应，又能限制肿瘤细胞周围药物的可用性，从而形成一种屏障。这种机制原则上应该限制肿瘤的扩张，但相反，它经常导致免疫系统对肿瘤细胞的识别受损。此外，MSC 与先天和适应性免疫系统抗肿瘤淋巴细胞之间的串扰强烈促使 TME 变得免疫抑制。事实上，MSC 可以触发几种类型的调节细胞的产生，这些细胞会阻断免疫反应，最终损害肿瘤细胞的清除。基于这些考虑，应该有可能通过作用于 TME 来促进抗肿瘤免疫反应。首先，我们将回顾涉及 MSC 介导的免疫反应调节的分子机制。其次，我们将重点介绍支持有可能将 TME 从免疫抑制转化为免疫刺激的实验数据，特别是针对 MSC。
