<i>Plasmodium</i> infection prevents recurrence and metastasis of hepatocellular carcinoma possibly via inhibition of the epithelial‑mesenchymal transition

Liang, Yun; Chen, Xiao; Tao, Zhu; Ma, Meng; Adah, Dickson; Li, Xiaofen; Dai, Lingling; Ding, Wenting; Fanuel, Songwe; Shu, Zhao; Li, Qin; Chen, Xiaoping; Zhang, Xiaowen

doi:10.3892/mmr.2021.12057

Cited by 9 publications

(12 citation statements)

References 47 publications

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“…Our murine cancer model studies have demonstrated that Plasmodium immunotherapy significantly promotes T cell infiltration into tumor tissue, downregulates PD-1 expression on T cells, upregulates perforin and granzyme B expression within T cells, and enhances tumor-specific cellular immune responses within tumors. In addition, Plasmodium infection significantly inhibit epithelium-mesenchymal transition (EMT), therefore prevent metastasis and relapse [74], and may also overcome drug resistance of tumor. On the basis of above mentioned mechanisms, we consider that Plasmodium immunotherapy may be a broadspectrum anticancer treatment.…”

Section: Systemic Ecological Counterattack Therapymentioning

confidence: 99%

The mechanisms of action of Plasmodium infection against cancer

Chen

et al. 2021

Cell Commun Signal

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Our murine cancer model studies have demonstrated that Plasmodium infection activates the immune system that has been inhibited by cancer cells, counteracts tumor immunosuppressive microenvironment, inhibits tumor angiogenesis, inhibits tumor growth and metastasis, and prolongs the survival time of tumor-bearing mice. Based on these studies, three clinical trials of Plasmodium immunotherapy for advanced cancers have been approved and are ongoing in China. After comparing the mechanisms of action of Plasmodium immunotherapy with those of immune checkpoint blockade therapy, we propose the notion that cancer is an ecological disease and that Plasmodium immunotherapy is a systemic ecological counterattack therapy for this ecological disease, with limited side effects and without danger to public health based on the use of artesunate and other measures. Recent reports of tolerance to treatment and limitations in majority of patients associated with the use of checkpoint blockers further support this notion. We advocate further studies on the mechanisms of action of Plasmodium infection against cancer and investigations on Plasmodium-based combination therapy in the coming future.

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Section: Systemic Ecological Counterattack Therapymentioning

confidence: 99%

The mechanisms of action of Plasmodium infection against cancer

Chen

et al. 2021

Cell Commun Signal

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“…Plasmodium infection also inhibits tumor angiogenesis by blocking the IGF-1/MMP9 signaling pathway of TAMs in tumor tissue through the metabolite hemozoin of the parasite ( 50 ). Plasmodium infection blocks the TGFβ/CCR10/PI3K/Akt/GSK-3β signaling pathway, thereby inhibiting epithelial–mesenchymal transition (EMT) of the cancer cells and preventing tumor metastasis and recurrence ( 53 , 54 ). Moreover, the material basis for suppressing EMT also exists within Plasmodium -associated exosomes (unpublished data).…”

Section: Discussionmentioning

confidence: 99%

From immune equilibrium to tumor ecodynamics

Chen

2024

Front. Oncol.

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ObjectivesThere is no theory to quantitatively describe the complex tumor ecosystem. At the same time, cancer immunotherapy is considered a revolution in oncology, but the methods used to describe tumors and the criteria used to evaluate efficacy are not keeping pace. The purpose of this study is to establish a new theory for quantitatively describing the tumor ecosystem, innovating the methods of tumor characterization, and establishing new efficacy evaluation criteria for cancer immunotherapy.MethodsBased on the mathematization of immune equilibrium theory and the establishment of immunodynamics in a previous study, the method of reverse immunodynamics was used, namely, the immune braking force was regarded as the tumor ecological force and the immune force was regarded as the tumor ecological braking force, and the concept of momentum in physics was applied to the tumor ecosystem to establish a series of tumor ecodynamic equations. These equations were used to solve the fundamental and applied problems of the complex tumor ecosystem.ResultsA series of tumor ecodynamic equations were established. The tumor ecological momentum equations and their component factors could be used to distinguish disease progression, pseudoprogression, and hyperprogression in cancer immunotherapy. On this basis, the adjusted tumor momentum equations were established to achieve the equivalence of tumor activity (including immunosuppressive activity and metabolic activity) and tumor volume, which could be used to calculate individual disease remission rate and establish new efficacy evaluation criteria (ieRECIST) for immunotherapy of solid tumor based on tumor ecodynamics. At the same time, the concept of moving cube-to-force square ratio and its expression were proposed to calculate the area under the curve of tumor ecological braking force of blood required to achieve an individual disease remission rate when the adjusted tumor ecological momentum was known.ConclusionsA new theory termed tumor ecodynamics emphasizing both tumor activity and tumor volume is established to solve a series of basic and applied problems in the complex tumor ecosystem. It can be predicted that the future will be the era of cancer immune ecotherapy that targets the entire tumor ecosystem.

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“…The author of this paper and colleagues have long been engaged in the research of Plasmodium infection against cancer. Through murine model studies, we have demonstrated that Plasmodium infection activates the host immune system, induces antitumor innate and adaptive immune responses (Chen et al, 2011;Liu et al, 2017;Pan et al, 2021), relieves tumor immunosuppressive microenvironment (Adah et al, 2019), inhibits tumor angiogenesis through a series of mechanisms (Yang et al, 2017;Qin et al, 2020;, inhibits cancer epithelial mesenchymal transformation (EMT) (Liang et al, 2021), and inhibits tumor growth and metastasis, therefore, significantly prolongs the life of tumor-bearing animals (Chen et al, 2021). Based on our research, clinical trials of Plasmodium immunotherapy for advanced cancer have been approved and are ongoing in China (NCT02786589, NCT03474822, and NCT03375983).…”

Section: Anticancer Mechanism Of Plasmodium Immunotherapy and Its Ind...mentioning

confidence: 99%

From immune equilibrium to immunodynamics

Chen

2022

Front. Microbiol.

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ObjectiveThe immunology field has long been short of a universally applicable theoretical model that can quantitatively describe the immune response, and the theory of immune equilibrium (balance) is usually limited to the interpretation of the philosophical significance of immune phenomena. Therefore, it is necessary to establish a new immunological theory, namely, immunodynamic theory, to reanalyze the immune response.MethodsBy quantifying the immune dynamic equilibrium as the ratio of positive and negative immune power, the immune dynamic equilibrium equation was established. Then, the area under the curve of the positive and negative immune power was assumed to be equal in the whole process of immune response (regardless of correct or not), and through thought experiments based on this key hypothesis, a series of new concepts and expressions were derived, to establish a series of immunodynamic equations.ResultsNew concepts of immune force and immune braking force and their expression equations, namely, the theoretical equations of immunodynamics, were derived through thought experiments, and the theoretical curves of immunodynamics were obtained according to these equations. Via the equivalent transformation of the theoretical equations and practical calculation of functional data, and by the methods of curve comparison and fitting, some practical equations of immunodynamics were established, and these practical equations were used to solve theoretical and practical problems that are related to the immunotherapy of infectious diseases and cancers.ConclusionThe traditional theory of immune equilibrium has been mathematized and transformed from a philosophical category into a new concrete scientific theory, namely the theory of immunodynamics, which solves the dilemma that the traditional theory cannot guide individualized medical practice for a long time. This new theory may develop into one of the core theories of immunology in the future.

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Plasmodium infection prevents recurrence and metastasis of hepatocellular carcinoma possibly via inhibition of the epithelial‑mesenchymal transition

Cited by 9 publications

References 47 publications

The mechanisms of action of Plasmodium infection against cancer

The mechanisms of action of Plasmodium infection against cancer

From immune equilibrium to tumor ecodynamics

From immune equilibrium to immunodynamics

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