Highlights on molecular mechanisms of MDSC-mediated immune suppression: paving the way for new working hypotheses
Samantha Solito1, Laura Pinton, Vera Damuzzo
1Department of Surgery, Oncology and Gastroenterology, Oncology and Immunology Section, University of Padova, Padova, Italy.
Abstract:
MDSCs have been recognized in the last years as tolerogenic cells, potentially dangerous in the context of neoplasia, since they are able to induce tolerance to a variety of anti-tumor effectors, including CD4(+) and CD8(+) T cells. It is currently believed that the origin of MDSCs is due to an arrest of the myeloid differentiation process caused by tumor-secreted factors released in the tumor microenvironment that are able to exert an effect on myeloid progenitors, rendering them unable to terminally differentiate into dendritic cells, granulocytes and macrophages. As a consequence, these immature myeloid cells acquire suppressive activity through the activation of several mechanisms, controlled by different transcription factors. The lack of consensus about the phenotypical characterization of human MDSCs is the result of the existence of different MDSC subsets, most likely depending on the tumor in which they expand and on the tumor specific cytokine cocktail driving their activation. This, in turn, might also influence the mechanisms of MDSC-mediated immune suppression. In this review article we address the role of tumor-derived factors (TDFs) in MDSC-recruitment and activation, discuss the complex heterogeneity of MDSC phenotype and analyze the crosstalk between activated T cells and MDSCs.
Insights
Myeloid-derived suppressor cells (MDSCs) promote tumor growth by suppressing anti-tumor immunity. Tumor-derived factors drive MDSC expansion and activation, leading to immune evasion in cancer.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Myeloid-derived suppressor cells (MDSCs) are key regulators of immune tolerance in cancer.
- MDSCs arise from arrested myeloid differentiation induced by tumor microenvironment factors.
- These immature cells suppress anti-tumor immune responses, including T cell activity.
Purpose of the Study:
- To review the role of tumor-derived factors (TDFs) in MDSC recruitment and activation.
- To discuss the phenotypic heterogeneity of human MDSCs.
- To analyze the interactions between T cells and MDSCs in cancer.
Main Methods:
- Literature review focusing on MDSCs in neoplasia.
- Analysis of mechanisms underlying MDSC-mediated immune suppression.
- Examination of tumor-specific factors influencing MDSC phenotype and function.
Main Results:
- TDFs are crucial for MDSC expansion and acquisition of suppressive functions.
- MDSC heterogeneity exists, varying with tumor type and cytokine milieu.
- MDSCs employ multiple mechanisms to inhibit anti-tumor T cell responses.
Conclusions:
- MDSCs represent a significant barrier to effective anti-cancer immunity.
- Understanding MDSC heterogeneity and activation is vital for developing immunotherapies.
- Targeting MDSCs or their activating factors may enhance anti-tumor responses.
