Journal
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2022.959300
Keywords
Toxoplasma gondii; immunotherapy; tumor suppression; avirulent T; gondii strains; CD8+T cell; dendritic cells (DCs)
Categories
Funding
- National Natural Science Foundation of China
- Science and Technology Planning Project of Guangdong Province
- Key Project of Guangzhou Science Research
- Basic Research Project of Key Laboratory of Guangzhou
- [81971954]
- [81772217]
- [2018A050506038]
- [201904020011]
- [202102100001]
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Toxoplasma gondii can reverse tumor-induced immunosuppression by activating the host's immune system, leading to tumor growth inhibition. This has important implications for the development of more effective immunotherapies.
Tumor cells can successfully escape the host immune attack by inducing the production of immunosuppressive cells and molecules, leading to an ineffective tumor treatment and poor prognosis. Although immunotherapies have improved the survival rate of cancer patients in recent years, more effective drugs and therapies still need to be developed. As an intracellular parasite, Toxoplasma gondii can trigger a strong Th1 immune response in host cells, including upregulating the expression of interleukin-12 (IL-12) and interferon-gamma (IFN-gamma). Non-replicating uracil auxotrophic strains of T. gondii were used to safely reverse the immunosuppression manipulated by the tumor microenvironment. In addition to the whole lysate antigens, T. gondii-secreted effectors, including Toxoplasma profilin, rhoptry proteins (ROPs), and dense granule antigens (GRAs), are involved in arousing the host's antigen presentation system to suppress tumors. When T. gondii infection relieves immunosuppression, tumor-related myeloid cells, including macrophages and dendritic cells (DCs), are transformed into immunostimulatory phenotypes, showing a powerful Th1 immune response mediated by CD8(+) T cells. Afterwards, they target and kill the tumor cells, and ultimately reduce the size and weight of tumor tissues. This article reviews the latest applications of T. gondii in tumor therapy, including the activation of cellular immunity and the related signal pathways, which will help us understand why T. gondii infection can restrain tumor growth.
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