Distinct mechanisms govern populations of myeloid-derived suppressor cells in chronic viral infection and cancer
| Autor: | Chih-Hang Anthony Tang, Kristin C. Hicks, Sergei I. Grivennikov, Chih-Chi Andrew Hu, Dmitry I. Gabrilovich, E. John Wherry, Fernanda Pilataxi, Shino Hanabuchi, Corinne Cayatte, Gozde Kar, Kathy Mulgrew, Aimee Landry, Evgenii N. Tcyganov, Brian Dougherty, Ayumi Hashimoto, Yulia Nefedova, David A Campbell, Susana Hayes, Wei Guo, Tim Slidel, Mohammed Alkhatim A. Ali, Jean Christophe Beltra |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Lymphocytic Choriomeningitis Biology Lymphocytic choriomeningitis Interferon-gamma Mice Immune system Cell Line Tumor Neoplasms Immune Tolerance medicine Animals Humans Lymphocytic choriomeningitis virus Mice Knockout Innate immune system ATF6 Myeloid-Derived Suppressor Cells Endoplasmic reticulum Cancer Neoplasms Experimental General Medicine Endoplasmic Reticulum Stress medicine.disease Mice Inbred C57BL Virus Diseases Tumor progression Chronic Disease Cancer research Myeloid-derived Suppressor Cell Female Transcriptome Research Article |
| Zdroj: | J Clin Invest |
| ISSN: | 1558-8238 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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