ABSTRACT
Regulatory T (Treg) cells, possess a strategic role in the maintenance of immune homeostasis, and their function has been closely linked to development of diverse pathologies including autoimmunity and cancer. Comprehensive studies in various disease contexts revealed an increased plasticity as a characteristic of Treg cells. Although Treg cell plasticity comes in various flavors, the major categories enclose the loss of Foxp3 expression, which is the master regulator of Treg cell lineage, giving rise to "ex-Treg" cells and the "fragile" Treg cells in which FOXP3 expression is retained but accompanied by the engagement of an inflammatory program and attenuation of the suppressive activity. Treg cell plasticity possess a tremendous therapeutic potential either by inducing Treg cell de-stabilization to promote anti-tumor immunity, or re-enforcing Treg cell stability to attenuate chronic inflammation. Herein, we review the literature on the Treg cell plasticity with lessons learned in autoimmunity and cancer and discuss challenges and open questions with potential therapeutic implications.
Subject(s)
Autoimmune Diseases/immunology , Autoimmunity , Cell Plasticity , Lymphocytes, Tumor-Infiltrating/immunology , Neoplasms/immunology , T-Lymphocytes, Regulatory/immunology , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/metabolism , Cell Lineage , Cytokines/metabolism , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Humans , Immunotherapy , Lymphocytes, Tumor-Infiltrating/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/therapy , Phenotype , Signal Transduction , T-Lymphocytes, Regulatory/metabolism , Tumor EscapeABSTRACT
Myeloid-derived suppressor cells (MDSC) are potent suppressor cells that accumulate in tumor microenvironment and inhibit anti-tumor responses. Assessment of cell-autonomous MDSC responses allows the precise characterization of MDSCs in various disease settings and elucidates the underlying mechanisms of MDSC-mediated immune suppression. Here we describe a protocol for the isolation of tumor infiltrating or splenic MDSC, as well as their subpopulations, from melanoma-inoculated mice using Fluorescent Activated Cell Sorting (FACS). We further provide protocols for investigation of the autophagy pathway and ex vivo assessment of MDSC suppressive function using lymph node responder cells. These assays allow a comprehensive characterization of MDSC in murine experimental models.
