Inhibition of Lewis Lung Carcinoma Growth by Toxoplasma gondii through Induction of Th1 Immune Responses and Inhibition of Angiogenesis

Abstract

Toxoplasma gondii is an obligate intracellular protozoan parasite that induces antitumor activity against certain types of cancers. However, little information is available regarding the immunologic mechanisms that regulate these effects. For this purpose, C57BL/6 mice were administered either the T. gondii Me49 strain orally or Lewis lung carcinoma (LLC) cells intramuscularly. Survival rates, tumor size, histopathology, and immune responses were determined for each group, and angiogenesis was evaluated by in vivo Matrigel plug assay. Toxoplasma-infected (TG-injected) mice survived the entire experimental period, whereas cancer cell-bearing (LLC-injected) mice died within six weeks. Mice injected with both T. gondii and cancer cells (TG/LLC-injected group) showed significantly increased survival rates, CD8+ T-cell percentages, IFN-γ mRNA expression levels, serum IgG2a titers, and CTL responses as compared to the LLC-injected mice. In addition, angiogenesis in the TG/LLC-injected mice was notably inhibited. These effects in TG/LCC-injected mice were similar or were increased by the addition of an adjuvant, Quil-A. However, TG/LLC-injected mice showed decreased percentages of CD4+ and CD8+ T-cells, IFN-γ mRNA expression levels, and serum IgG1 and IgG2a titers as compared to TG-injected mice. Taken together, our results demonstrate that T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and antiangiogenic activity.

Lipoxin A4 and Its Analogue Suppress the Tumor Growth of Transplanted H22 in Mice: The Role of Antiangiogenesis

“…Important clues indicate that LXs, the first family of endogenous "braking signals" in inflammation identified in vivo (5), might interfere with tumor angiogenesis (16,17). HCC is a highly vascular tumor, and angiogenesis is believed to play a crucial role in its development (32).…”

“…Importantly, it was recently identified that tumor growth was inhibited concomitantly with suppressed angiogenesis during acute Toxoplasma gondii infection in mice (16,17). These observations suggest that LXs might be involved in tumor angiogenesis, but the governing mechanisms are unknown.…”

Effect of two hydatid cyst antigens on the growth of melanoma cancer in C57/black mice

“…According to previous researches, some parasites have capability of antitumor activities (Darani and Yousefi 2012;Kim et al 2007;López et al 2010;Oikonomopoulou et al 2013;Pidherney et al 1993;Plumelle et al 1997) and so parasite antigens have been considered as possible targets for cancer immunotherapy (Darani and Yousefi 2012). In a retrospective study with a large population it has been shown that the prevalence of hydatid cysts in patients with cancer was significantly lower than the control group (Akgül et al 2003).…”

Effects of Toxoplasma gondii and Toxocara canis Antigens on WEHI-164 Fibrosarcoma Growth in a Mouse Model

“…Various factors such as air pollution and dietary habits may be responsible for the increase in the cancer mortality following control of infectious and parasitic diseases. However, there are raising scientific evidences indicating that parasitic or bacterial infections induce antitumor activity against certain types of cancers [3][4][5][6][7][8]. For example, anticancer activity of Trypanozoma cruzi parasites has been demonstrated [3], and it has been shown that Bacillus Calmette Guerin (BCG) is an effective immunotherapy for carcinoma of the bladder, as reviewed by Herr et al [8].…”