Induction of myeloid-derived suppressor cells by tumor exosomes

By Xiaoyu Xiang, A. Poliakov, Cunren Liu, Yuelong Liu, Zhong-bin Deng, Jianhua Wang, Ziqiang Cheng, Spandan V. Shah, Guihua Wang, Liming Zhang and 3 more. International Journal of Cancer, 2009

602 citations recorded by the source corpus.

Myeloid‐derived suppressor cells (MDSCs) promote tumor progression. The mechanisms of MDSC development during tumor growth remain unknown. Tumor exosomes (T‐exosomes) have been implicated to play a role in immune regulation, however the role of exosomes in the induction of MDSCs is unclear. Our previous work demonstrated that exosomes isolated from tumor cells are taken up by bone marrow myeloid cells. Here, we extend those findings showing that exosomes isolated from T‐exosomes switch the differentiation pathway of these myeloid cells to the MDSC pathway (CD11b+Gr‐1+). The resulting cells exhibit MDSC phenotypic and functional characteristics including promotion of tumor growth. Furthermore, we demonstrated that in vivo MDSC mediated promotion of tumor progression is dependent on T‐exosome prostaglandin E2 (PGE2) and TGF‐β molecules. T‐exosomes can induce the accumulation of MDSCs expressing Cox2, IL‐6, VEGF, and arginase‐1. Antibodies against exosomal PGE2 and TGF‐β block the activity of these exosomes on MDSC induction and therefore attenuate MDSC‐mediated tumor‐promoting ability. Exosomal PGE2 and TGF‐β are enriched in T‐exosomes when compared with exosomes isolated from the supernatants of cultured tumor cells (C‐exosomes). The tumor microenvironment has an effect on the potency of T‐exosome mediated induction of MDSCs by regulating the sorting and the amount of exosomal PGE2 and TGF‐β available. Together, these findings lend themselves to developing specific targetable therapeutic strategies to reduce or eliminate MDSC‐induced immunosuppression and hence enhance host antitumor immunotherapy efficacy. © 2008 Wiley‐Liss, Inc.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/3ae009355b516faf9ee56f2132295b2dea457866

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In Immunology

1. C. Théry
2. A. Labani-Motlagh
3. Mehrnoush Ashja-Mahdavi
4. T. Whiteside
5. A. Loskog
6. W. Stoorvogel
7. G. Raposo

In Molecular Biology

1. T. Whiteside
2. C. Théry
3. A. Llorente
4. W. Stoorvogel
5. M. Wood
6. P. Vader
7. María Yáñez-Mó
8. Imre Mäger

In Oncology

1. E. Song
2. Lin Zhang
3. Dihua Yu
4. T. Whiteside

Citations in the corpus

• Exosomes in cancer development, metastasis, and immunity (2019, background): “EVs released by HER2+ cells that are resistant to HER2-targeted drugs contained immune-regulated proteins TGFβ1 and PDL1, which made cells that had been sensitive to HER2-targeted drugs resistant.”
• Exosomes in cancer: small particle, big player (2015, background): “Tumor cell-derived exosomes switch the differentiation of myeloid cells to myeloid-derived suppressor cells (MDSCs) and induce accelerated lung metastasis in a MyD88-dependent manner [61, 62].”
• The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses (2020, background): “In this in vivo experiment, tumor-derived exosomes injected in mice recruited CD11b Gr-1 cells to tumor and were taken up by them (116).”
• Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper (2017, background): “myeloid derived suppressor cells (MDSCs), experimental evidence supports the latter: EV uptake actively changes MDSCs to become more immunosuppressive [226,227]”
• Cancer exosomes trigger fibroblast to myofibroblast differentiation. (2010, positive): “While much of the research within the exosome field continues to focus on immunomodulatory functions (5, 7, 8, 11, 31, 36), a small number of reports show that cancer exosomes may well be capable of altering the functions of nonimmune cells within the tumor microenvironment.”
• Exosome-Based Cell-Cell Communication in the Tumor Microenvironment (2018, background): “This finding was reinforced by the involvement of MyD88, a molecule involved in the propagation of signals generated by the TLR family and production of IL-6, TNF-α, and CCL2, in the recruitment and activity of MDSCs by tumor-derived exosomes (Liu et al., 2010).”
• Classification, Functions, and Clinical Relevance of Extracellular Vesicles (2012, background): “…of myeloid cells to myeloidderived suppressor cells, immature myeloid cells that have the ability to suppress T-cell activation and thereby promote tumor progression, induce the expression of TGF- and prostacyclin E2 within tumor-derived exosomes (Xiang et al., 2009; Liu et al., 2010).”
• Biological properties of extracellular vesicles and their physiological functions (2015, background): “Also, tumour-derived EVs were found to use a TGFbmediatedmechanism to induce regulatory Tcells (153,154) andmyeloid suppressor cells (155).”