Paving the Road to Tumor Development and Spreading: Myeloid-Derived Suppressor Cells are Ruling the Fate

Abstract

Cancer development is dependent on intrinsic cellular changes as well as inflammatory factors in the tumor macro and microenvironment. The inflammatory milieu nourishes the tumor and contributes to cancer progression. Numerous studies, including ours, have demonstrated that the tumor microenvironment is immunosuppressive, impairing the anticancer immune responses. Chronic inflammation was identified as the key process responsible for this immunosuppression via induction of immature myeloid-derived suppressor cells (MDSCs). Upon a prolonged immune response, MDSCs are polarized toward immunosuppressive cells meant to control the exacerbated immune response. In cancer, the chronic inflammatory response renders the MDSCs harmful. Polarized MDSCs suppress T-cells and natural killer cells, as well as antigen-presenting cells, abrogating the beneficial immune response. These changes in the immunological milieu could also lead to high frequency of mutations, enhanced cancer cell stemness, and angiogenesis, directly supporting tumor initiation, growth, and spreading. The presence of MDSCs in cancer poses a serious obstacle in a variety of immune-based therapies, which rely on the stimulation of antitumor immune responses. Cumulative data, including our own, suggest that the selection of an appropriate and effective anticancer therapy must take into consideration the host’s immune status as well as tumor-related parameters. Merging biomarkers for immune monitoring into the traditional patient’s categorization and follow-up can provide new predictive and diagnostic tools to the clinical practice. Chronic inflammation and MDSCs could serve as novel targets for therapeutic interventions, which can be combined with conventional cancer treatments such as chemotherapy, radiotherapy, and cancer cell-targeted and immune-based therapies. Intervention in environmental and tumor-specific inflammatory mechanisms will allow better clinical management of cancer toward more efficient treatment.

Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock

“…Of note, MDSCs are phenotypically plastic, which allows them a diverse functionality in response to their environmental conditions, but also creates the potential for future immunomodulating therapies 22 . As observed in cancer immunotherapy 36 , targeting MDSCs could become a component in multimodality therapy aimed at reversing detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term morbidity and mortality 37 .…”

Autoimmunity and Inflammation in Myelodysplastic Syndromes

“…TGF-β, IL-10) [51]. Interestingly, chronic immune stimulation that was implicated in the pathogenesis of MDS [3] promotes the accumulation of myeloid-derived suppressor cells [52]. …”

Moving Immune Checkpoint Blockade in Thoracic Tumors beyond NSCLC

“…35 Most importantly, the tumor itself exerts protumoral features of myeloid and lymphoid elements to maintain a permissive environment for growth and spread. 36 Tumor-associated macrophages and neutrophils, 37 dendritic cells, 38 myeloid-derived suppressor cells 39 and lymphocytic (regulatory B and T cells) 40,41 populations harboring inhibitory activity contribute to immune impairment. The malignant microenvironment acts in parallel, both favoring cancer cell growth and inhibiting immune effectors, mainly by abnormal tumor vascularization and high pro-angiogenic factors (e.g.…”