Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma

Dar, Asif Amin; Patil, Rushikesh Sudam; Pradhan, Trupti; Chaukar, Devendra A; D’Cruz, Anil; Chiplunkar, Shubhada V.

doi:10.1007/s00262-020-02523-w

Cited by 36 publications

(24 citation statements)

References 46 publications

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“…The suppressive capacity of these cells appears to be enhanced as they infiltrate tumors, pointing to the crucial role of the TME in modulating their function [107]. MDSCs are characterized by their ability to suppress the immune response through different mechanisms, including the inhibition of T cell functionality associated with the expression and activity of arginase-1 [108, 109], promoting the differentiation of Tregs [110], and the differentiation of pro-tumor TAMs [111, 112]. Recent work in humans also showed that MDSCs can promote angiogenesis via MMP-9 secretion [113].…”

Section: The Immune System and Cancermentioning

confidence: 99%

Immune System Efficiency in Cancer and the Microbiota Influence

2021

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The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.

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Section: The Immune System and Cancermentioning

confidence: 99%

Immune System Efficiency in Cancer and the Microbiota Influence

2021

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“…Th17 cells are another group of immunosuppressive cells characterized by the production of IL-17, which cripple T lymphocyte cytotoxicity. MDSCs induce inducible nitric oxide synthase (iNOS) production in T cells, favoring Th17 cells proliferation (Jayakumar and Bothwell, 2019;Dar et al, 2020). Conversely, Tregs were also observed to contribute to the development of MDSCs.…”

Section: Construction Of An Immunosuppressive Campmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy

Shi

et al. 2021

Front. Cell Dev. Biol.

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T lymphocytes function as major players in antigen-mediated cytotoxicity and have become powerful tools for exploiting the immune system in tumor elimination. Several types of T cell-based immunotherapies have been prescribed to cancer patients with durable immunological response. Such strategies include immune checkpoint inhibitors, adoptive T cell therapy, cancer vaccines, oncolytic virus, and modulatory cytokines. However, the majority of cancer patients still failed to take the advantage of these kinds of treatments. Currently, extensive attempts are being made to uncover the potential mechanism of immunotherapy resistance, and myeloid-derived suppressor cells (MDSCs) have been identified as one of vital interpretable factors. Here, we discuss the immunosuppressive mechanism of MDSCs and their contributions to failures of T cell-based immunotherapy. Additionally, we summarize combination therapies to ameliorate the efficacy of T cell-based immunotherapy.

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“…Elevated levels of IL-6, IL-10, TNF-α, IL-1β, IL-8, TGF-β, PGE 2 , and VEGF present in sera of OSCC patients helps in regulating immunosuppressive functions of MDSC. The mechanism used by MDSCs to suppress T cell proliferation and reduce levels of key signaling molecule CD3-ζ chain is through the expression of STAT3 regulated Arg 1 and IDO [65]. The therapeutic approach based on inhibiting STAT3 in MDSC is of clinical relevance since inhibition of STAT3 signaling in OSCC patients will not only stall the EGFR mediated tumor progression but also aid in revitalizing the antitumor immunity by inhibiting the production and function of MDSCs.…”

Section: Tregsmentioning

confidence: 99%

Immunosuppressive microenvironment in oral cancer: implications for cancer immunotherapy

et al. 2021

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Head and neck squamous cell carcinoma (HNSCC) is a relatively widespread cancer with high mortality rates. Many patients with locally advanced disease are treated with combinations of surgery, radiation, and chemotherapy, while others are considered incurable and develop recurrent/metastatic(R/M) disease. Despite these treatment modalities, the 5-year survival rate of HNSCC has remained at 50% due to limited treatment options in patients with recurrent disease. Immunotherapy has been shown to induce durable responses in R/M patients, but only a minority of patients currently respond. A major hurdle in tumor immunotherapy is identifying the non-responders and markers to predict resistance in patients who at first responded to the therapy. In HNSCC patients, the tumor microenvironment (TME) assumes a vital role to either diminish or augment immune responses. There is an urgent need for extensive studies to be undertaken to better understand how tumor cells escape immune surveillance and resist immune attack. In this review, the impact of TME on the efficiency of immunotherapy, addressing the factors that mediate therapy resistance are highlighted. The composition of the TME encompassing the immunosuppressive cells including myeloid-derived suppressor cell (MDSC), regulatory T cells (Treg), mesenchymal stem cell (MSC), cancer-associated fibroblast (CAF), and tumor-associated macrophages (TAMs) and intrinsic factors like hypoxia, reactive oxygen species (ROS),extracellular matrix (ECM), angiogenesis, and epithelial-mesenchymal transition (EMT), how this debilitates immunosurveillance, and also discuss existing and potential strategies aimed at targeting these cellular and molecular TME components are reviewed. Understanding the interactions between the TME and immunotherapy is not only important in dissevering the mechanisms of action of immunosuppression but also offers scope for developing newer strategies to improve the competence of current immunotherapies.

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Myeloid-derived suppressor cells impede T cell functionality and promote Th17 differentiation in oral squamous cell carcinoma

Cited by 36 publications

References 46 publications

Immune System Efficiency in Cancer and the Microbiota Influence

Immune System Efficiency in Cancer and the Microbiota Influence

Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy

Immunosuppressive microenvironment in oral cancer: implications for cancer immunotherapy

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