Abstract
Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.
Highlights
Introduction iationsThe term “anti-tumor immunity” refers to the innate and adaptive immune response elicited against tumor antigens [1]
CD4+T helper (Th) cells orchestrate the anti-tumor immune response through the production of interleukin (IL)-2, which increases the proliferation of CD8+ cytotoxic T lymphocytes (CTLs) and through the secretion of interferon gamma (IFN-γ), which induces the generation of the anti-tumorigenic M1 phenotype in tumor-infiltrated macrophages (TAMs) [1,3]
By using a murine metastatic model of lung cancer, we demonstrated that intravenously injected BM-Mesenchymal stem cells (MSCs) significantly augmented lung cancer metastasis by down-regulating the anti-tumor immune response [29]
Summary
MSCs (CA-MSCs)) and exogenously administered MSCs promoted tumor growth by: MSCs (CA-MSCs)) and exogenously administered MSCs promoted tumor growth by: (i). (i) preventing the DC-dependent activation of naive T cells, (ii) inducing the alternative preventing the DC-dependent activation of naive T cells, (ii) inducing the alternative actiactivation of TAMs, (iii) modulating cytokine production in T helper cells, (iv) downvation of TAMs, (iii) modulating cytokine production in T helper cells, (iv) down-regulatregulating the cytotoxicity of CTLs and NK cells and (v) promoting the generation and ing the cytotoxicity of CTLs and NK cells and (v) promoting the generation and expansion expansion of Tregs and MDSCs (Figure 1). Of Tregs and MDSCs [14,15,16,17,18,19,20,21].
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