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Distinct mechanisms govern populations of myeloid-derived suppressor cells in chronic viral infection and cancer.
Tcyganov, Evgenii N; Hanabuchi, Shino; Hashimoto, Ayumi; Campbell, David; Kar, Gozde; Slidel, Timothy Wf; Cayatte, Corinne; Landry, Aimee; Pilataxi, Fernanda; Hayes, Susana; Dougherty, Brian; Hicks, Kristin C; Mulgrew, Kathy; Tang, Chih-Hang Anthony; Hu, Chih-Chi Andrew; Guo, Wei; Grivennikov, Sergei; Ali, Mohammed-Alkhatim A; Beltra, Jean-Christophe; Wherry, E John; Nefedova, Yulia; Gabrilovich, Dmitry I.
Afiliação
  • Tcyganov EN; Immunology, Microenvironment, and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
  • Hanabuchi S; AstraZeneca, Gaithersburg, Maryland, USA.
  • Hashimoto A; Immunology, Microenvironment, and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
  • Campbell D; AstraZeneca, Gaithersburg, Maryland, USA.
  • Kar G; AstraZeneca, Gaithersburg, Maryland, USA.
  • Slidel TW; AstraZeneca, Translational Medicine, Research and Early Development, Oncology Research & Development, Cambridge, United Kingdom.
  • Cayatte C; AstraZeneca, Translational Medicine, Research and Early Development, Oncology Research & Development, Cambridge, United Kingdom.
  • Landry A; AstraZeneca, Gaithersburg, Maryland, USA.
  • Pilataxi F; AstraZeneca, Gaithersburg, Maryland, USA.
  • Hayes S; AstraZeneca, Gaithersburg, Maryland, USA.
  • Dougherty B; AstraZeneca, Gaithersburg, Maryland, USA.
  • Hicks KC; AstraZeneca, Gaithersburg, Maryland, USA.
  • Mulgrew K; AstraZeneca, Gaithersburg, Maryland, USA.
  • Tang CA; AstraZeneca, Gaithersburg, Maryland, USA.
  • Hu CA; Immunology, Microenvironment, and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
  • Guo W; Immunology, Microenvironment, and Metastasis Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
  • Grivennikov S; Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
  • Ali MA; Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
  • Beltra JC; Department of Systems Pharmacology and Translational Therapeutics and.
  • Wherry EJ; Department of Systems Pharmacology and Translational Therapeutics and.
  • Nefedova Y; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Gabrilovich DI; Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Clin Invest ; 131(16)2021 08 16.
Article em En | MEDLINE | ID: mdl-34228641
Myeloid-derived suppressor cells (MDSCs) are major negative regulators of immune responses in cancer and chronic infections. It remains unclear if regulation of MDSC activity in different conditions is controlled by similar mechanisms. We compared MDSCs in mice with cancer and lymphocytic choriomeningitis virus (LCMV) infection. Chronic LCMV infection caused the development of monocytic MDSCs (M-MDSCs) but did not induce polymorphonuclear MDSCs (PMN-MDSCs). In contrast, both MDSC populations were present in cancer models. An acquisition of immune-suppressive activity by PMN-MDSCs in cancer was controlled by IRE1α and ATF6 pathways of the endoplasmic reticulum (ER) stress response. Abrogation of PMN-MDSC activity by blockade of the ER stress response resulted in an increase in tumor-specific immune response and reduced tumor progression. In contrast, the ER stress response was dispensable for suppressive activity of M-MDSCs in cancer and LCMV infection. Acquisition of immune-suppressive activity by M-MDSCs in spleens was mediated by IFN-γ signaling. However, it was dispensable for suppressive activity of M-MDSCs in tumor tissues. Suppressive activity of M-MDSCs in tumors was retained due to the effect of IL-6 present at high concentrations in the tumor site. These results demonstrate disease- and population-specific mechanisms of MDSC accumulation and the need for targeting different pathways to achieve inactivation of these cells.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Viroses / Células Supressoras Mieloides / Neoplasias Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Viroses / Células Supressoras Mieloides / Neoplasias Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article