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Journal of autoimmunity v.85, 2017년, pp.117 - 125   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Myeloid suppressor cells in cancer and autoimmunity

Sica, Antonio    (Department of Pharmaceutical Sciences, Università  ); Massarotti, Marco    (del Piemonte Orientale “Amedeo Avogadro”, via Bovio 6, Novara, Italy   );
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    Abstract A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression. Tumor-associated myeloid cells comprise heterogeneous populations acting systemically (myeloid-derived suppressor cells/MDSCs) and/or locally in the tumor microenvironment (MDSCs and tumor-associated macrophages/TAMs). Both populations promote cancer cell proliferation and survival, angiogenesis and lymphangiogenesis and elicit immunosuppression through different pathways, including the expression of immunosuppressive cytokines and checkpoint inhibitors. Several evidences have demonstrated that myeloid cells can express different functional programs in response to different microenvironmental signals, a property defined as functional plasticity. The opposed extremes of this functional flexibility are generally represented by the classical macrophage activation, which identifies inflammatory and cytotoxic M1 polarized macrophages, and the alternative state of macrophage activation, which identifies M2 polarized anti-inflammatory and immunosuppressive macrophages. Functional skewing of myeloid cells occurs in vivo under physiological and pathological conditions, including cancer and autoimmunity. Here we discuss how myeloid suppressor cells can on one hand support tumor growth and, on the other, limit autoimmune responses, indicating that their therapeutic reprogramming can generate opportunities in relieving immunosuppression in the tumor microenvironment or reinstating tolerance in autoimmune conditions. Highlights Skewing of myeloid cell polarization orchestrates the onset and resolution phases of the inflammatory and immune responses. Skewing of myeloid cells occurs in vivo under physiological and pathological conditions, including cancer and autoimmunity. Myeloid suppressor cells can on one hand support tumor growth and, on the other, limit autoimmune responses. Therapeutic reprogramming of myeloid cells can relieve immunosuppression in cancer or reinstate tolerance in autoimmunity.


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