Cellular mesenchymal-epithelial transition factor (c-MET), also known as hepatocyte growth factor receptor (HGFR), is a crucial receptor tyrosine kinase implicated in various solid tumors, including lung, breast, and liver cancers. The concomitant expression of c-MET and PD-L1 in tumors, such as hepatocellular carcinoma, highlights their prognostic significance and connection to therapeutic resistance. Cancer-associated fibroblasts and mesenchymal stromal cells produce hepatocyte growth factor (HGF), activating c-MET signaling in tumor cells and myeloid-derived suppressor cells (MDSC). This activation leads to metabolic reprogramming and increased activity of enzymes like glutaminase (GLS), indoleamine 2,3-dioxygenase (IDO), and arginase 1 (ARG1), depleting essential amino acids in the tumor microenvironment that are vital for effector immune cell function. This review highlights the interplay between tumor cells and myeloid-derived suppressor cells (MDSCs) that create an immunosuppressive environment while providing targets for c-MET-focused immunotherapy. It emphasizes the clinical implications of c-MET inhibition on the behavior of immune cells such as neutrophils, macrophages, T cells, and NK cells. It explores the potential of c-MET antagonism combined with immunotherapeutic strategies to enhance cancer treatment paradigms. This review also discusses the innovative cancer immunotherapies targeting c-MET, including chimeric antigen receptor (CAR) therapies, monoclonal antibodies, and antibody-drug conjugates, while encouraging the development of a comprehensive strategy that simultaneously tackles immune evasion and enhances anti-tumor efficacy further to improve the clinical prognoses for patients with c-MET-positive malignancies. Despite the challenges and variability in efficacy across different cancer subtypes, continued research into the molecular mechanisms and the development of innovative therapeutic strategies will be crucial.
There has been a great interest in myeloid-derived suppressor cells (MDSCs) due to their biological functions in tumor-mediated immune escape by suppressing antitumor immune responses. These cells arise from altered myelopoiesis in response to the tumor-derived factors. The most recognized function of MDSCs is suppressing anti-tumor immune responses by impairing T cell functions, and these cells are the most important players in cancer dissemination and metastasis. Therefore, understanding the factors and the mechanism of MDSC differentiation, expansion, and recruitment into the tumor microenvironment can lead to its control. However, most of the studies only defined MDSCs with no further characterization of granulocytic and monocytic subsets. In this review, we discuss the mechanisms by which specific MDSC subsets contribute to cancers. A better understanding of MDSC subset development and the specific molecular mechanism is needed to identify treatment targets. The understanding of the specific molecular mechanisms responsible for MDSC accumulation would enable more precise therapeutic targeting of these cells.
Autoimmunity is the assault of immune response towards self-antigens, resulting to inflammation and tissue injury. It is staged into three phases and caused by malfunction of immune tolerance. In our body, immune tolerance is synchronized by several immunosuppressor cells such as regulatory T cells and B cells as well as myeloid-derived suppressor cells, which are prominently dysregulated in autoimmunity. Hence, targeting these cell populations serve as a significant potential in the therapy of autoimmunity. Nanotechnology with its advantageous properties is shown to be a remarkable tool as drug delivery system in this field. This review focused on the development of therapeutics in autoimmune diseases utilizing various nanoparticles formulation based on two targeting approaches in autoimmunity, passive and active targeting. Lastly, this review outlined the approved present nanomedicines as well as in clinical evaluations and issues regarding the lack of translation of these nanomedicines into the market, despite the abundant of positive experimental observations.