Article ; Online: Anti-oxidative Amino Acid L-ergothioneine Modulates the Tumor Microenvironment to Facilitate Adjuvant Vaccine Immunotherapy.
2019 Volume 10, Page(s) 671
Abstract: Cancer vaccines consist of a tumor-associated antigen (TAA) and adjuvant. These vaccines induce and activate proliferation of TAA-specific cytotoxic T lymphocytes (CTLs), suppressing tumor growth. The therapeutic efficacy of TAA-specific CTLs depends on ... ...
| Abstract | Cancer vaccines consist of a tumor-associated antigen (TAA) and adjuvant. These vaccines induce and activate proliferation of TAA-specific cytotoxic T lymphocytes (CTLs), suppressing tumor growth. The therapeutic efficacy of TAA-specific CTLs depends on the properties of tumor microenvironment. The environments make immunosuppressive by function of regulatory T cells and tumor-associated myeloid cells; thus, regulation of these cells is important for successful cancer immunotherapy. We report here that L-ergothioneine (EGT) with the adjuvant Toll-like receptor 2 (TLR2) ligand modulated suppressive microenvironments to be immune-enhancing. EGT did not augment DC-mediated CTL priming or affect CTL activation in draining lymph node and spleen. However, EGT decreased the immuno-suppressive function of tumor-associated macrophages (TAMs). TLR2 stimulation accompanied with EGT administration downregulated expression of PD-L1, CSF-1R, arginase-1, FAS ligand, and TRAIL in TAMs, reflecting reduction of CTL suppression. An anti-oxidative thiol-thione residue of EGT was essential to dampening CTL suppression. The effect was specific to the thiol-thione residue of EGT because no effect was observed with another anti-oxidant N-acetyl-L-cysteine (NAC). A CTL-suppressive environment made by TLR2 is relieved to be improved by the addition of EGT, which may ameliorate the efficacy of vaccine immunotherapy. |
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| MeSH term(s) | Animals ; Antioxidants/chemistry ; Antioxidants/pharmacology ; Cancer Vaccines/immunology ; Cell Line, Tumor ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Ergothioneine/chemistry ; Ergothioneine/pharmacology ; Female ; Humans ; Immunization ; Immunotherapy ; Ligands ; Lymphocytes, Tumor-Infiltrating ; Mice ; Models, Molecular ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; T-Lymphocytes, Cytotoxic/drug effects ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/metabolism ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 6/metabolism ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Xenograft Model Antitumor Assays |
| Chemical Substances | Antioxidants ; Cancer Vaccines ; Ligands ; TLR2 protein, human ; TLR6 protein, human ; Toll-Like Receptor 2 ; Toll-Like Receptor 6 ; Ergothioneine (BDZ3DQM98W) |
| Language | English |
| Publishing date | 2019-04-04 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2019.00671 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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