Cellules myéloïdes suppressives et cancer : une nouvelle cible thérapeutique

Chalmin, Fanny; Mignot, Grégoire; Ghiringhelli, François

doi:10.1051/medsci/2010266-7576

Cited by 5 publications

(5 citation statements)

References 11 publications

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“…Furthermore, Stat3 regulates Myc expression by increasing the duration of occupancy of C/EBPβ on the Myc promoter [54]. Recently, it has been shown that MDSCs isolated from cancer patients treated with amiloride, which inhibits exosome formation, had reduced suppressive functions [98, 99]. …”

Section: Signaling Pathways In Mdsc Functionmentioning

confidence: 99%

Signaling pathways involved in MDSC regulation

Trikha

Carson

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

156

140

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The immune system has evolved mechanisms to protect the host from the deleterious effects of inflammation. The generation of immune suppressive cells like myeloid derived suppressor cells (MDSCs) that can counteract T cell responses represents one such strategy. There is an accumulation of immature myeloid cells or MDSCs in bone marrow (BM) and lymphoid organs under pathological conditions such as cancer. MDSCs represent a population of heterogeneous myeloid cells comprising of macrophages, granulocytes and dendritic cells that are at early stages of development. Although, the precise signaling pathways and molecular mechanisms that lead to MDSC generation and expansion in cancer remains to be elucidated. It is widely believed that perturbation of signaling pathways involved during normal hematopoietic and myeloid development under pathological conditions such as tumorogenesis contributes to the development of suppressive myeloid cells. In this review we discuss the role played by key signaling pathways such as PI3K, Ras, Jak/Stat and TGFb during myeloid development and how their deregulation under pathological conditions can lead to the generation of suppressive myeloid cells or MDSCs. Targeting these pathways should help in elucidating mechanisms that lead to the expansion of MDSCs in cancer and point to methods for eliminating these cells from the tumor microenvironment.

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Section: Signaling Pathways In Mdsc Functionmentioning

confidence: 99%

Signaling pathways involved in MDSC regulation

Trikha

Carson

2014

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

156

140

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“…When expressed at the surface of tumour-derived exosomes (TDE), indeed, Hsp70 may promote myeloid-derived suppressor cells (MDSCs) activity and restrain tumour immune surveillance of CD8 + cells [247,248]. TDE-associated Hsp70 binds Toll-like receptor 2 (TLR2) on MDSC plasma membrane and triggers MSDC immunosuppressive function through IL-6 production and STAT3 activation [249]. Tumour growth and drug resistance are both increased in TDE-presenting Hsp70-expressing cells, whereas exosomes depletion by efflux pump inhibitors reduces extracellular Hsp70 levels and enhances chemotherapy efficacy [250].…”

Section: Role Of Inducible Hsp70 Chaperone In Lysosome-mediated Cell mentioning

confidence: 99%

Inducible Hsp70 in the Regulation of Cancer Cell Survival: Analysis of Chaperone Induction, Expression and Activity

Zorzi

Bonvini

2011

Cancers

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Understanding the mechanisms that control stress is central to realize how cells respond to environmental and physiological insults. All the more important is to reveal how tumour cells withstand their harsher growth conditions and cope with drug-induced apoptosis, since resistance to chemotherapy is the foremost complication when curing cancer. Intensive research on tumour biology over the past number of years has provided significant insights into the molecular events that occur during oncogenesis, and resistance to anti-cancer drugs has been shown to often rely on stress response and expression of inducible heat shock proteins (HSPs). However, with respect to the mechanisms guarding cancer cells against proteotoxic stresses and the modulatory effects that allow their survival, much remains to be defined. Heat shock proteins are molecules responsible for folding newly synthesized polypeptides under physiological conditions and misfolded proteins under stress, but their role in maintaining the transformed phenotype often goes beyond their conventional chaperone activity. Expression of inducible HSPs is known to correlate with limited sensitivity to apoptosis induced by diverse cytotoxic agents and dismal prognosis of several tumour types, however whether cancer cells survive because of the constitutive expression of heat shock proteins or the ability to induce them when adapting to the hostile microenvironment remains to be elucidated. Clear is that tumours appear nowadays more “addicted” to heat shock proteins than previously envisaged, and targeting HSPs represents a powerful approach and a future challenge for sensitizing tumours to therapy. This review will focus on the anti-apoptotic role of heat shock 70kDa protein (Hsp70), and how regulatory factors that control inducible Hsp70 synthesis, expression and activity may be relevant for response to stress and survival of cancer cells.

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“…Ainsi, de nombreuses cellules immunosuppressives localisées dans le microenvironnement tumoral contribuent aux échecs de différentes stratégies vaccinales [5]. Enfin, contrairement aux pathogènes, les cellules cancéreuses proviennent du soi et, pour le système immunitaire, ne constituent donc pas une menace per se.…”

Section: (➜)unclassified

Mobiliser l’immunité innée dans le traitement des cancers

Garaude

2013

Med Sci (Paris)

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Cellules myéloïdes suppressives et cancer : une nouvelle cible thérapeutique

Cited by 5 publications

References 11 publications

Signaling pathways involved in MDSC regulation

Signaling pathways involved in MDSC regulation

Inducible Hsp70 in the Regulation of Cancer Cell Survival: Analysis of Chaperone Induction, Expression and Activity

Mobiliser l’immunité innée dans le traitement des cancers

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