Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target

Abstract

Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid cells that can suppress antitumor immune responses mediated by T and natural killer cells and promote tumor growth. They are major contributors to ICI resistance and play a crucial role in creating an immunosuppressive tumor microenvironment. Therefore, targeting MDSCs is considered a promising strategy to improve the therapeutic efficacy of ICIs. This Review describes the mechanism of MDSC-mediated immune suppression, preclinical and clinical studies on MDSC targeting, and potential strategies for inhibiting MDSC functions to improve melanoma immunotherapy.

Targeting TREM1 augments antitumor T cell immunity by inhibiting myeloid-derived suppressor cells and restraining anti–PD-1 resistance

“…It is likely that the reduction of MDSC populations and their immunosuppressive function observed in the Trem1 –/– TME is one of the potential mechanisms for enhancing CD8 + T cell expansion and the expression of PD-1 on those cells, making them more susceptible to anti-PD-1 treatment. Previous studies demonstrated that reprogramming the immunosuppressive capacity of MDSCs or inhibiting its biogenesis ( 83 ) enhances the response to anti-PD-1 therapy in melanoma ( 84 ) and colorectal cancers ( 85 , 86 ). In the current study, combining TREM1 inhibition and anti-PD-1 ICB induced complete tumor regression.…”

Recent advances in understanding the immune microenvironment in ovarian cancer

“…However, in inflammation or the TME, the differentiation of MDSCs is disrupted by signaling molecules such as cytokines and growth factors, resulting in their accumulation. MDSCs suppress immune responses by inhibiting T-cell activation and proliferation, promoting regulatory Treg development and function, and modulating other immune cell activities ( 101 ). Their accumulation is a key mechanism enabling tumors to evade immune surveillance and fuel tumor growth.…”

Understanding the Tumor Microenvironment in Melanoma Patients with In-Transit Metastases and Its Impacts on Immune Checkpoint Immunotherapy Responses

“…Meanwhile, the phenotypic features shared among various myeloid populations greatly reduce drug target specificity. The application of single-cell technologies, thus, becomes essential to accurately define the diverse phenotypic states and enhance the targeting accuracy of immunotherapeutic inhibitors [101].…”