scholarly journals Blocking Migration of Polymorphonuclear Myeloid-Derived Suppressor Cells Inhibits Mouse Melanoma Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 726
Author(s):  
Christopher Groth ◽  
Ludovica Arpinati ◽  
Merav E. Shaul ◽  
Nina Winkler ◽  
Klara Diester ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Checkpoint Inhibitors ◽  
Suppressor Cells ◽  
Receptor Expression ◽  
Myeloid Derived Suppressor Cells ◽  
Melanoma Progression ◽  
Relative Contribution ◽  
Immunosuppressive Tumor Microenvironment ◽  
Metastatic Sites

Background: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression. Methods: Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas. Results: Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells. Conclusions: We provide evidence for the tumor−promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.

scholarly journals Immunomodulation by Inflammation during Liver and Gastrointestinal Tumorigenesis and Aging

2021 ◽  
Vol 22 (5) ◽  
pp. 2238
Author(s):  
Nao Nagai ◽  
Yotaro Kudo ◽  
Daisuke Aki ◽  
Hayato Nakagawa ◽  
Koji Taniguchi
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Antitumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cytotoxic T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Immunosuppressive Tumor Microenvironment ◽  
Pro Inflammatory Cytokines

Chronic inflammation is thought to promote tumorigenesis and metastasis by several mechanisms, such as affecting tumor cells directly, establishing a tumor-supporting microenvironment, enhancing tumor angiogenesis, and suppressing antitumor immunity. In this review, we discuss the recent advances in our understanding of how inflammation induces the immunosuppressive tumor microenvironment, such as increasing the level of pro-inflammatory cytokines, chemokines, and immunosuppressive molecules, inducing immune checkpoint molecules and cytotoxic T-cell exhaustion, and accumulating regulatory T (Treg) cells and myeloid-derived suppressor cells (MDSCs). The suppression of antitumor immunity by inflammation is especially examined in the liver and colorectal cancer. In addition, chronic inflammation is induced during aging and causes age-related diseases, including cancer, by affecting immunity. Therefore, we also discuss the age-related diseases regulated by inflammation, especially in the liver and colon.

scholarly journals Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 561 ◽  
Author(s):  
Andrew M. K. Law ◽  
Fatima Valdes-Mora ◽  
David Gallego-Ortega
Keyword(s):  
Cancer Progression ◽  
Therapeutic Target ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Myeloid Derived Suppressor Cells ◽  
Cancer Treatments ◽  
Patient Response

The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.

Liposomal microparticle injection can induce myeloid-derived suppressor cells (MDSC)-like cells in vivo

2017 ◽  
Vol 39 (3) ◽  
pp. 140-147 ◽  
Author(s):  
Hiroshi Azuma ◽  
Yoichiro Yoshida ◽  
Hironori Takahashi ◽  
Emi Ishibazawa ◽  
Hiroya Kobayashi ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

scholarly journals Astaxanthin Treatment Induces Maturation and Functional Change of Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 350
Author(s):  
Seong Mun Jeong ◽  
Yeon-Jeong Kim
Keyword(s):  
Mhc Class Ii ◽  
Target Genes ◽  
Suppressor Cells ◽  
Functional Change ◽  
Related Factor ◽  
Mrna Levels ◽  
Myeloid Derived Suppressor Cells ◽  
Antitumor Effects

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells which accumulate in stress conditions such as infection and tumor. Astaxanthin (ATX) is a well-known antioxidant agent and has a little toxicity. It has been reported that ATX treatment induces antitumor effects via regulation of cell signaling pathways, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2) signaling. In the present study, we hypothesized that treatment with ATX might induce maturation of MDSCs and modulate their immunosuppressive activity. Both in vivo and in vitro treatment with ATX resulted in up-regulation of surface markers such as CD80, MHC class II, and CD11c on both polymorphonuclear (PMN)-MDSCs and mononuclear (Mo)-MDSCs. Expression levels of functional mediators involved in immune suppression were significantly reduced, whereas mRNA levels of Nrf2 target genes were increased in ATX-treated MDSCs. In addition, ATX was found to have antioxidant activity reducing reactive oxygen species level in MDSCs. Finally, ATX-treated MDSCs were immunogenic enough to induce cytotoxic T lymphocyte response and contributed to the inhibition of tumor growth. This demonstrates the role of ATX as a regulator of the immunosuppressive tumor environment through induction of differentiation and functional conversion of MDSCs.

scholarly journals Calreticulin Fragment 39-272 Promotes B16 Melanoma Malignancy through Myeloid-Derived Suppressor Cells In Vivo

2017 ◽  
Vol 8 ◽  
Author(s):  
Xiao-Yan He ◽  
Fang-Yuan Gong ◽  
Yong Chen ◽  
Zhe Zhou ◽  
Zheng Gong ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
B16 Melanoma ◽  
Myeloid Derived Suppressor Cells

scholarly journals Atovaquone Suppresses Triple-Negative Breast Tumor Growth by Reducing Immune-Suppressive Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5150
Author(s):  
Nehal Gupta ◽  
Shreyas Gaikwad ◽  
Itishree Kaushik ◽  
Stephen E. Wright ◽  
Maciej M. Markiewski ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cancer Progression ◽  
Breast Tumor ◽  
Triple Negative ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
In Vivo Models ◽  
Ribosomal Protein S19

A major contributing factor in triple-negative breast cancer progression is its ability to evade immune surveillance. One mechanism for this immunosuppression is through ribosomal protein S19 (RPS19), which facilitates myeloid-derived suppressor cells (MDSCs) recruitment in tumors, which generate cytokines TGF-β and IL-10 and induce regulatory T cells (Tregs), all of which are immunosuppressive and enhance tumor progression. Hence, enhancing the immune system in breast tumors could be a strategy for anticancer therapeutics. The present study evaluated the immune response of atovaquone, an antiprotozoal drug, in three independent breast-tumor models. Our results demonstrated that oral administration of atovaquone reduced HCC1806, CI66 and 4T1 paclitaxel-resistant (4T1-PR) breast-tumor growth by 45%, 70% and 42%, respectively. MDSCs, TGF-β, IL-10 and Tregs of blood and tumors were analyzed from all of these in vivo models. Our results demonstrated that atovaquone treatment in mice bearing HCC1806 tumors reduced MDSCs from tumor and blood by 70% and 30%, respectively. We also observed a 25% reduction in tumor MDSCs in atovaquone-treated mice bearing CI66 and 4T1-PR tumors. In addition, a decrease in TGF-β and IL-10 in tumor lysates was observed in atovaquone-treated mice with a reduction in tumor Tregs. Moreover, a significant reduction in the expression of RPS19 was found in tumors treated with atovaquone.

Myeloid immunosuppressive state as a predictor of rapidly progressive phenotype and poor survival in advanced non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20594-e20594
Author(s):  
Sally CM Lau ◽  
Lisa W Le ◽  
Sze Wah Samuel Chan ◽  
Elliot Charles Smith ◽  
Malcolm Ryan ◽  
...  
Keyword(s):  
T Regulatory Cells ◽  
Checkpoint Inhibitors ◽  
Smoking Status ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Logistic Regression Models ◽  
Immature Myeloid Cells ◽  
Pre Treatment ◽  
Highly Correlated ◽  
Nsclc Patients

e20594 Background: Immune subpopulations within the tumor microenvironment (TME) play a central role in determining response to checkpoint inhibitors. Myeloid derived suppressor cells, a heterogeneous population of immature myeloid cells, have a predominantly immunosuppressive role by stimulating T regulatory cells. We hypothesize that elevated myeloid-to-lymphocyte measures in the peripheral blood predict for greater numbers of myeloid derived suppressor cells in the TME and worse outcomes. Methods: In advanced NSCLC patients who received immunotherapy between 2010-2018, baseline characteristics collected retrospectively included age, sex, histology, stage, smoking status, ethnicity, PD-L1 expression and tumor genotype. Pre-treatment neutrophil/lymphocyte (NLR) and monocyte/lymphocyte ratios (MLR) were log transformed and analyzed using cox and logistic regression models. Results: Among 219 eligible patients, a high NLR was associated with shorter time-to-treatment-failure (HR 1.38, 95%CI 1.09-1.75, p = 0.008) and poorer OS (HR 1.62, 95%CI 1.23-2.14, p < 0.001), independent of PD-L1 levels. Disproportionate increases in NLR and MLR were highly correlated (Spearman’s rho = 0.78). Further, higher NLR (p = 0.09) or MLR (p = 0.06) tended to associate with best overall response (BOR) to immunotherapy, with higher rates of progressive disease (PD) and lower rates of clinical response. A high NLR (p = 0.01) and MLR (p = 0.02) were associated with a rapidly progressive phenotype defined by PD as the BOR and duration of therapy ≤2 months. This remained significant after adjusting for confounders in a multivariate model (p = 0.03 for NLR and p = 0.03 for MLR). No associations were observed between high myeloid counts and other clinical prognostic factors such as liver metastases. Conclusions: A myeloid immunosuppressive state characterized by a disproportionate increase in peripheral immune myeloid populations is significantly associated with primary refractory disease, rapidly progressive phenotype, and poorer survival. Further investigation into myeloid mediated mechanisms of resistance is warranted.

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