Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model

Bahwal, Said Ahmed; Chen, Jane J; Lilin, E; Hao, Taofang; Chen, Jiancong; Carruthers, Vern B.; Lai, Jiaming; Zhou, Xingwang

doi:10.1007/s00432-022-04036-8

Cited by 11 publications

(10 citation statements)

References 55 publications

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“…Furthermore, RH-Δ cps can arouse long-term immunity to disseminated pancreatic cancer and prevent the recurrence of highly aggressive tumors to some extent ( Sanders et al., 2016 ). Intraperitoneal injection of the recombinant RH strain with uridine phosphorylase gene and ompdc knockout together with anti-PD-1 antibody can markedly reduce the immunosuppressive myeloid-derived suppression in pancreatic tumor-bearing mice ( Bahwal et al., 2022 ). In situ inoculation of RH-Δ ompdc mutant in 4T1 murine breast tumor can restrict tumor growth and lung metastasis ( Xu et al., 2021 ).…”

Section: Avirulent T Gondii Strains Applied In Tum...mentioning

confidence: 99%

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Chen

Liao

Peng

2022

Front. Cell. Infect. Microbiol.

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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-γ (IFN-γ). 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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Section: Avirulent T Gondii Strains Applied In Tum...mentioning

confidence: 99%

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Chen

Liao

Peng

2022

Front. Cell. Infect. Microbiol.

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“…Of note, while the survival against the primary tumor does not depend on CD4 + T cells, the distribution and stability of circulating tumor‐specific IgG provide a protective effect against tumor re‐challenge. However, further research is needed to fully understand the relationship between memory immune cells and circulating antibodies in the mechanism of action of the cps mutant of T. gondii for cancer treatment 54,57,117 …”

Section: Pancreatic Cancermentioning

confidence: 99%

A potential cure for tumor‐associated immunosuppression by Toxoplasma gondii

Lotfalizadeh,

Sadr,

Morovati

et al. 2023

Cancer Reports

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BackgroundRecently, immunotherapy has become very hopeful for cancer therapy. Cancer treatment through immunotherapy has excellent specificity and less toxicity than conventional chemoradiotherapy. Pathogens have been used in cancer immunotherapy for a long time. The current study aims to evaluate the possibility of Toxoplasma gondii (T. gondii) as a probable treatment for cancers such as melanoma, breast, ovarian, lung, and pancreatic cancer.Recent findingsNonreplicating type I uracil auxotrophic mutants of T. gondii can stimulate immune responses against tumors by reverse immunosuppression at the cellular level. T. gondii can be utilized to research T helper 1 (Th1) cell immunity in intracellular infections. Avirulent T. gondii uracil auxotroph vaccine can change the tumor's immunosuppression and improve the production of type 1 helper cell cytokines, i.e., Interferon‐gamma (IFN‐γ) and Interleukin‐12 (IL‐12) and activate tumor‐related Cluster of Differentiation 8 (CD8+) T cells to identify and destroy cancer cells. The T. gondii profilin protein, along with T. gondii secreted proteins, have been found to exhibit promising properties in the treatment of various cancers. These proteins are being studied for their potential to inhibit tumor growth and enhance the effectiveness of cancer therapies. Their unique mechanisms of action make them valuable candidates for targeted interventions in ovarian cancer, breast cancer, pancreatic cancer, melanoma, and lung cancer treatments.ConclusionIn summary, the study underscores the significant potential of harnessing T. gondii, including its diverse array of proteins and antigens, particularly in its avirulent form, as a groundbreaking approach in cancer immunotherapy.

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“…Moreover, non-replicating Toxoplasma uracil auxotrophs (NATUA) and Carbomyl phosphate synthetase (cps) gene knockout strains show that these parasites can enhance the T cell infiltration and improve the tumor immunogenicity of the tumor. For instance, combination therapy of attenuated T. gondii NRTUA with anti-programmed death-1 (PD-1) led to elevation of CD8+ T cell infiltration mediated by dendritic cell-secreted IL-12 and to tumor-specific IFN-γ production in the PDAC tumor microenvironment [ 96 ]. CD8+ T cell infiltration in the TME will be reduced with the depletion of IL-12.…”

Section: Improving the Microenvironmentmentioning

confidence: 99%

“…CD8+ T cell infiltration in the TME will be reduced with the depletion of IL-12. Combination therapy of NRTUA with anti-PD-1 also significantly reduced tumor weight in PDAC solid tumor [ 96 ].…”

Section: Improving the Microenvironmentmentioning

confidence: 99%

Anti-Tumor Effect of Parasitic Protozoans

Ding

et al. 2022

Bioengineering

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The immune system may aberrantly silence when against “altered self”, which consequently may develop into malignancies. With the development of tumor immunology and molecular biology, the deepened understanding of the relationship between parasites and tumors shifts the attitude towards parasitic pathogens from elimination to utilization. In recent years, the antitumor impact implemented by protozoan parasites and the derived products has been confirmed. The immune system is activated and enhanced by some protozoan parasites, thereby inhibiting tumor growth, angiogenesis, and metastasis in many animal models. In this work, we reviewed the available information on the antitumor effect of parasitic infection or induced by parasitic antigen, as well as the involved immune mechanisms that modulate cancer progression. Despite the fact that clinical trials of the protozoan parasites against tumors are limited and the specific mechanisms of the effect on tumors are not totally clear, the use of genetically modified protozoan parasites and derived molecules combined with chemotherapy could be an important element for promoting antitumor treatment in the future.

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Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model

Cited by 11 publications

References 55 publications

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

Toxoplasma gondii infection possibly reverses host immunosuppression to restrain tumor growth

A potential cure for tumor‐associated immunosuppression by Toxoplasma gondii

Anti-Tumor Effect of Parasitic Protozoans

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