Available online 5 May 2023, 108544
Author links open overlay panel, AbstractThe ongoing conflict regarding the affiliation of Toxoplasma gondii to cancer; whether an inducer or a suppressor needs to be resolved. Human epidemiological studies oscillate without attaining a firm ground. Some studies confirmed the detection of high seroprevalence of anti-Toxoplasma antibodies in different cancer patients without further justification whether being causation, co-incidences, or part of opportunistic infections. Others reported a state of resistance to cancer accompanying low titer of anti-Toxoplasma antibody. Worthwhile, preclinical experimental work confirmed the antineoplastic potency of Toxoplasma. Thus, further investigational research is essential to validate the potential application of Toxoplasma as a promising cancer immunotherapeutic vaccine candidate. In this paper, we present a review of this issue by examining epidemiological and preclinical experimental studies that explored the linkage between Toxoplasma gondii and cancer<i.></i> We consider this review an important step towards shedding a light on this mysterious link and a stepping-stone for potential research work addressing Toxoplasma as a cancer suppressor rather than a cancer inducer.
Section snippetsDatabase searchIn order to examine the most relevant literature used in this review, we searched electronic database in PubMed, ScienceDirect, Google Scholar, and Egyptian knowledge bank using the following keywords “Pathogens and cancer”, “Toxoplasma and cancer”, “Toxoplasma as cancer inducer”, “Toxoplasma as anti-cancerous” and “Toxoplasma in cancer immunotherapy”. Many confounding factors probably affect the interpretation of the results of the epidemiological studies of the prevalence of toxoplasmosis in
Toxoplasma: with or against cancer?The debate is still ongoing, and the balance is sometimes tipping toward cancer and on many other occasions tipping against cancer. T. gondii is an obligate intracellular pathogen, belonging to the phylum Apicomplexa (Schluter and Barragan, 2019). Theoretically speaking, T. gondii is assumed to behave like other intracellular pathogens; to promote cancer via a prolonged state of inflammation, hence accumulating oncogenic mutations (Knoll et al., 2018; Mostafa et al., 2018). On contrary, a low
Immune response to Toxoplasma gondiiAs an intracellular pathogen and in an immunocompetent host, a group of Pro-inflammatory cytokines (IFN-γ, IL-1, IL-12, IL-18) are essential master keys in the initiation of both the innate and the acquired immune response to counteract the proliferating Toxoplasma gondii. A potent cell-mediated immune response with the production of interferon-gamma (IFN-γ) usually dominates and is vital in controlling T. gondii with a limited role of the humoral immune response. However, to support the growth
Host cell invasion by toxoplasma: is it a must?The molecular influence of Toxoplasma invasion on the host cell remains uncertain. Alterations in cell signaling and molecular pathways influencing cancer development have been reported (stimulating solid tumors while inhibiting hematological cancers) (Caner, 2021). However, tachyzoites’ proteins (rhoptry and dense granule effector proteins) secreted before and after host cell invasion were shown to modulate host immune response favoring an antineoplastic role of Toxoplasma [62].
Whether host
ConclusionHuman epidemiological studies are still skeptical and lack any firm foundation that demonstrates a causal relationship between Toxoplasma and cancer development. Multiple points should be considered, First, the evidence of the existence of toxoplasmosis as an opportunistic infection in cancer patients is of no doubt highlighting the necessity of close supervision of cancer patients. Second; the risk of coincidence of toxoplasmosis in cancer patients needs more concern when dealing with data.
FundingThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Consent to participateNot applicable.
Consent to publishNot applicable.
Uncited referenceGuallar-Garrido and Julián, 2020.
Declaration of competing interestThe authors declare that they have no conflict of interest.
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