The role of tumor-derived exosomes in tumor immune escape: A concise review

Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

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Platelets in cancer development and diagnosis

Biochemical Society Transactions ◽

10.1042/bst20180159 ◽

2018 ◽

Vol 46 (6) ◽

pp. 1517-1527 ◽

Cited By ~ 9

Author(s):

Annalisa Contursi ◽

Rosalia Grande ◽

Melania Dovizio ◽

Annalisa Bruno ◽

Rosa Fullone ◽

...

Keyword(s):

Cancer Detection ◽

Immune Escape ◽

Genetic Material ◽

Antiplatelet Agents ◽

Therapeutic Drug ◽

Target Cells ◽

Tumor Immune Escape ◽

New Strategy ◽

Tumor Drugs

Platelets are involved in the development and progression of cancer through several mechanisms. Platelet activation at the site of tissue damage contributes to the initiation of a cascade of events which promote tumorigenesis. In fact, platelets release a wide array of proteins, including growth and angiogenic factors, lipids and extracellular vesicles rich in genetic material, which can mediate the induction of phenotypic changes in target cells, such as immune, stromal and tumor cells, and promote carcinogenesis and metastasis formation. Importantly, the role of platelets in tumor immune escape has been described. These lines of evidence open the way to novel strategies to fight cancer based on the use of antiplatelet agents. In addition to their ability to release factors, platelets are able of up-taking proteins and genetic material present in the bloodstream. Platelets are like ‘sentinels’ of the disease state. The evaluation of proteomics and transcriptomics signature of platelets and platelet-derived microparticles could represent a new strategy for the development of biomarkers for early cancer detection and/or therapeutic drug monitoring in cancer chemotherapy. Owing to the ability of platelets to interact with cancer cells and to deliver their cargo, platelets have been proposed as a ‘biomimetic drug delivery system’ for anti-tumor drugs to prevent the occurrence of off-target adverse events associated with the use of traditional chemotherapy.

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MMP-9-cleaved osteopontin isoform mediates tumor immune escape by inducing expansion of myeloid-derived suppressor cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2017.10.009 ◽

2017 ◽

Vol 493 (4) ◽

pp. 1478-1484 ◽

Cited By ~ 14

Author(s):

Lijuan Shao ◽

Bo Zhang ◽

Lingxiong Wang ◽

Liangliang Wu ◽

Quancheng Kan ◽

...

Keyword(s):

Immune Escape ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape

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Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells

Case Reports in Obstetrics Gynecology and Reproductive ◽

10.31487/j.crogr.2020.03.03 ◽

2020 ◽

pp. 1-5

Author(s):

Takuma Hayashi ◽

Kaoru Abiko ◽

Takuma Hayashi ◽

Ken Yamaguchi ◽

Masaki Mandai ◽

...

Keyword(s):

Ovarian Cancer ◽

Immune Escape ◽

Suppressor Cells ◽

Exploratory Laparotomy ◽

Myeloid Derived Suppressor Cells ◽

Antitumor Effects ◽

Response To Chemotherapy ◽

Programmed Cell Death 1 ◽

Cancer Immunotherapeutic ◽

Immune Escape Mechanisms

Diagnosis by biopsy is difficult in the ovary, since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the omentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favourable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PDligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

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Increased Expression of Myeloid-Derived Suppressor Cells in Patients with HBV-Related Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2020/6527192 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Tianyu Li ◽

Xinyu Zhang ◽

Zhuo Lv ◽

Li Gao ◽

Huimin Yan

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Systemic Inflammation ◽

Cd8 T Cells ◽

Immune Escape ◽

Suppressor Cells ◽

Tumor Burden ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape ◽

Indirect Bilirubin

Background and Aim. Myeloid-derived suppressor cells (MDSCs) have attracted attention due to their important role in tumor immune escape. Several studies have investigated the involvement of MDSCs into hepatocellular carcinoma (HCC); however, due to the difference of MDSC phenotype, patient types, and sample source among the studies, the results were inconsistent and controversial. The present study aimed to confirm the expression and clinical significance of MDSCs in HBV-related HCC patients. Methods. The percentages of MDSCs, IFN-γ-producing CD4 and CD8 T cells in the peripheral blood of HCC patients, chronic hepatitis B (CHB) patients, and healthy controls (HC) were determined by flow cytometry. The serum concentrations of IL-10 and TNF-α were determined by ELISA. The association of the percentages of MDSCs with tumor burden, liver function parameters, systemic inflammation-related indexes, and IFN-γ-producing T cells was assessed. Results. The percentages of MDSCs and PMN-MDSCs were significantly higher in HCC patients than those in CHB patients and HC. The level of MDSCs was correlated with indirect bilirubin and prealbumin, as well as systemic inflammation response index, monocyte/lymphocyte ratio, and monocyte counts. The frequency of IFN-γ-producing CD8 T cells of HCC patients was lower than that of HC. However, there was no relationship between MDSCs and IFN-γ-producing CD8 T cells. The level of IL-10 in HCC patients was significantly higher than that in CHB patients. Conclusion. MDSCs seem to play an important role in the process leading from chronic HBV infection to HCC. Early inhibiting these cells could affect tumor progression.

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Immunotherapy Targeting Myeloid-Derived Suppressor Cells (MDSCs) in Tumor Microenvironment

Frontiers in Immunology ◽

10.3389/fimmu.2020.585214 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xidan Gao ◽

Hongshu Sui ◽

Shang Zhao ◽

Xingmei Gao ◽

Yanping Su ◽

...

Keyword(s):

Immune System ◽

Tumor Microenvironment ◽

Immune Escape ◽

Suppressor Cells ◽

Tumor Immunotherapy ◽

Therapeutic Effects ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape ◽

New Directions ◽

Immature Myeloid Cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate in tumor-bearing hosts to reduce T cells activity and promote tumor immune escape in the tumor microenvironment (TME). The immune system in the TME can be stimulated to elicit an anti-tumor immune response through immunotherapy. The main theory of immunotherapy resides on the plasticity of the immune system and its capacity to be re-educated into a potent anti-tumor response. Thus, MDSCs within the TME became one of the major targets to improve the efficacy of tumor immunotherapy, and therapeutic strategies for tumor MDSCs were developed in the last few years. In the article, we analyzed the function of tumor MDSCs and the regulatory mechanisms of agents targeting MDSCs in tumor immunotherapy, and reviewed their therapeutic effects in MDSCs within the TME. Those data focused on discussing how to promote the differentiation and maturation of MDSCs, reduce the accumulation and expansion of MDSCs, and inhibit the function, migration and recruitment of MDSCs, further preventing the growth, invasion and metastasis of tumor. Those investigations may provide new directions for cancer therapy.

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Myeloid-derived suppressor cells regulate the immunosuppressive functions of PD-1−PD-L1+ Bregs through PD-L1/PI3K/AKT/NF-κB axis in breast cancer

Cell Death and Disease ◽

10.1038/s41419-021-03745-1 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Min Liu ◽

Feng Wei ◽

Jian Wang ◽

Wenwen Yu ◽

Meng Shen ◽

...

Keyword(s):

Breast Cancer ◽

B Cells ◽

Immune Escape ◽

Suppressor Cells ◽

Regulatory Mechanisms ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape ◽

Cell Immunity ◽

Immunosuppressive Tumor Microenvironment ◽

Cancer Tissues

AbstractMyeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells that are closely related to tumor immune escape, but the mechanism by which MDSCs regulate B cells has not been elucidated. Our previous studies revealed that breast cancer-derived MDSCs could induce a group of PD-1−PD-L1+ Bregs with immunosuppressive functions. Here, we reported that blocking PD-1/PD-L1 interaction between MDSCs and B cells could reverse the immunosuppressive functions of PD-1−PD-L1+ Bregs. The activation of PI3K/AKT/NF-κB signaling pathway is essential for PD-1−PD-L1+ Bregs to exert immunosuppressive effects. MDSCs activated the PI3K/AKT/NF-κB pathway in B cells via the PD-1/PD-L1 axis. Furthermore, inhibition of PD-1/PD-L1 or PI3K/AKT signaling suppressed both tumor growth and the immunosuppressive functions of PD-1−PD-L1+ Bregs. Dual suppression of PD-1/PD-L1 and PI3K/AKT exerted better antitumor effect. Finally, MDSCs and PD-1−PD-L1+ Bregs were colocalized in breast cancer tissues and PD-1−PD-L1+ Bregs were positively correlated with poor prognosis. Thus, MDSC-educated PD-1−PD-L1+ Bregs and their regulatory mechanisms could contribute to the immunosuppressive tumor microenvironment. Our study proposes a novel mechanism for MDSC-mediated regulation of B cell immunity, which might shed new light on tumor immunotherapy.+

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Abstract 4063: The oncogenic cell cycle-related kinase promotes tumor immune escape via modulation of myeloid-derived suppressor cells in hepatocellular carcinoma

10.1158/1538-7445.am2015-4063 ◽

2015 ◽

Author(s):

Jingying Zhou ◽

Alfred Sze Lok Cheng ◽

Zhiwei Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Immune Escape ◽

Suppressor Cells ◽

Myeloid Derived Suppressor Cells ◽

Tumor Immune Escape

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501 VISTA regulates the differentiation and suppressive function of myeloid-derived suppressor cells

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0501 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A536-A536

Author(s):

Juan Dong ◽

Cassandra Gilmore ◽

Hieu Ta ◽

Keman Zhang ◽

Sarah Stone ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Signaling Pathways ◽

Immune Checkpoint ◽

Suppressor Cells ◽

Myeloid Cell ◽

Myeloid Derived Suppressor Cells ◽

Checkpoint Protein ◽

Suppressive Function

BackgroundV-domain immunoglobulin suppressor of T cell activation (VISTA) is a B7 family inhibitory immune checkpoint protein and is highly expressed on myeloid cells and T cells.1 VISTA acts as both an inhibitory ligand when expressed on antigen-presenting cells and a receptor when expressed on T cells. Our recent study has shown that VISTA is a myeloid cell-specific immune checkpoint and that blocking VISTA can reprogram suppressive myeloid cells and promote a T cell-stimulatory tumor microenvironment.2 In this study, we further demonstrate that VISTA blockade directly alters the differentiation and the suppressive function of myeloid-derived suppressor cells (MDSC).MethodsFlow cytometry was performed to examine VISTA expression on MDSCs in multiple murine tumor models including the B16BL6 melanoma model, MC38 colon cancer model, and the KPC pancreatic cancer models. To examine the role of VISTA in controlling the differentiation and suppressive function of MDSCs, we cultured wild type (WT) and VISTA.KO bone marrow progenitor cells with GM-CSF and IL-6 to induce BM -derived MDSCs.ResultsOur preliminary results show that VISTA is highly expressed on M-MDSCs in B16BL6, MC38 and KPC tumors. In BM-derived MDSCs, VISTA deletion significantly altered the signaling pathways and the differentiation of MDSCs. Multiple inflammatory signaling pathways were downregulated in VISTA KO MDSCs, resulting in decreased production of cytokines such as IL1 and chemokines such as CCL2/4/9, as well as significantly impaired their ability to suppress the activation of CD8+ T cells. The loss of suppressive function in VISTA KO MDSCs is correlated with significantly reduced expression of iNOS. To validate the results from BM-MDSCs, we sorted CD11b+CD11c-Ly6C+Ly6G- M-MDSCs and CD11b+CD11c-Ly6G+ G-MDSCs from B16BL6 tumor tissues and tested the ability of a VISTA-blocking mAb to reverse the suppressive effects of tumor-derived MDSCs. Our results show that blocking VISTA impaired the suppressive function of tumor-derived M-MDSC but not G-MDSCs.ConclusionsTaken together, these results demonstrate a crucial role of VISTA in regulating the differentiation and function of MDSCs, and that blocking VISTA abolishes MDSC-mediated T cell suppression, thereby boosting.Ethics ApprovalAll in vivo studies were reviewed and approved by Institutional Animal Care and Use Committee (Approval number 2019-2142).ReferencesXu W, Hire T, Malarkannan, S. et al. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 2018;15:438–446.Xu W, Dong J, Zheng Y, et al. Immune-checkpoint protein VISTA regulates antitumor immunity by controlling myeloid cell-mediated inflammation and immunosuppression. Cancer Immunol Res 2019;7:1497–510.

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