title: Listeria monocytogenes (Lm)-LLO immunotherapies reduce the immunosuppressive activity of myeloid-derived suppressor cells and regulatory T cells in the tumor microenvironment.
abstract: Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) are major components of the immune suppressive cells that potentially limit the effectiveness of an immunotherapy-based treatment. Both of these suppressive cell types have been shown to expand in tumor models and promote T-cell dysfunction that in turn favors tumor progression. This study demonstrates that Listeria monocytogenes (Lm)-LLO immunotherapies effect on the suppressive ability of MDSC and Treg in the tumor microenvironment (TME), resulting in a loss in the ability of these cells to suppress T cells. This alteration of immunosuppression in the TME was an inherent property of all Lm-LLO immunotherapies tested and was independent of the tumor model. The virtually total loss in the suppressive ability of these cells in the TME was linked to the reduction in the expression of arginase I in MDSC and IL-10 in Treg. The results presented here provide insight into a novel mechanism of Lm-LLO immunotherapies that potentially contributes to therapeutic antitumor responses.
authors.affiliation: *Advaxis Inc., Princeton, NJ †Novartis Institutes for Biomedical Research, Cambridge, MA.
authors.forename: Anu
authors.initials: A
authors.lastname: Wallecha
authors.forename: Reshma
authors.initials: R
authors.lastname: Singh
authors.forename: Inga
authors.initials: I
authors.lastname: Malinina
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D016753:Interleukin-10; C544448:Arg1 protein, mouse; D001119:Arginase; C038705:hlyA protein, Listeria monocytogenes