Suppression of the growth and metastasis of mouse melanoma by Taenia crassiceps and Mesocestoides corti tapeworms

Abstract

Cancer is still one of the leading causes of death, with an estimated 19.3 million new cases every year. Our paper presents the tumor-suppressing effect of Taenia crassiceps and Mesocestoides corti on B16F10 melanoma, the intraperitoneal application of which followed the experimental infection with these tapeworms, resulting in varying degrees of effectiveness in two strains of mice. In the case of M. corti-infected ICR mice, a strong tumor growth suppression occurred, which was accompanied by a significant reduction in the formation of distant metastases in the liver and lung. Tapeworm-infected C57BL/6J mice also showed a suppression of tumor growth and, in addition, the overall survival of infected C57BL/6J mice was significantly improved. Experiments with potential cross-reaction of melanoma and tapeworm antigens with respective specific antibodies, restimulation of spleen T cells, or the direct effect of tapeworm excretory-secretory products on melanoma cells in vitro could not explain the phenomenon. However, infections with T. crassiceps and M. corti increased the number of leukocytes possibly involved in anti-tumor immunity in the peritoneal cavity of both ICR and C57BL/6J mice. This study unveils the complex interplay between tapeworm infections, immune responses, and melanoma progression, emphasizing the need for further exploration of the mechanisms driving observed tumor-suppressive effects.

Keywords: Mesocestoides; Taenia; cancer; melanoma; metastasis; suppression; tapeworm.

Figure 1

The suppressive effect of tapeworm infection on melanoma. The overall survival of C57BL/6J mice infected with T. crassiceps and M. corti (each at n = 10) shows significant improvement in both cases of tapeworm infection compared to mice injected with only melanoma when analyzed with the Log-rank test (A). The weight of peritoneal tumors reveals a trend of suppression on their growth (n = 7), showing a greater decrease of peritoneal tumors in M. corti infections of C57BL/6J mice after analysis with Kruskal-Willis test with Dunn’s multiple comparisons (B). *** (p ≤ 0.001), ns (no significance).

Figure 2

Suppression of melanoma tumor growth in mice infected with tapeworms. In mice injected with only melanoma (A, D), the entirety of the peritoneal cavity was filled with masses of tumors (1), while only few smaller tumors (2) were found in mice infected with T. crassiceps (B, E) or M. corti (C, F). T. crassiceps cysticerci (3), free M. corti tetrathyridia (4), M. corti tetrathyridia embedded in liver parenchyma (5). (A–C) are C57BL/6J mice, (D–F) are ICR mice.

Figure 3

Histological evaluation of melanoma metastasis. B16F10 cells (1) were found to invade the liver (A) and lungs (E) of ICR mice without any tapeworm infection, while none were found within the liver (C, D) or lungs (G, H) of ICR mice infected also with T. crassiceps M. corti. Zoomed-in areas of the liver (B) and the lungs (F) with melanoma.

Figure 4

The growth of tapeworm larvae in the peritoneal cavity. Graph (A) shows that there is no difference in the growth curves of T. crassiceps between the C57BL/6J and ICR mouse strains, while the growth of M. corti (B) is slower in ICR mice compared to C57BL/6J mice. Each timepoint group consisted of n = 3, at a total of 5 groups per infection and mouse strain. A two-way ANOVA was utilized to compare the growth curves. ns (no significance), * (p ≤ 0.05).

Figure 5

Antibody response to tapeworm and melanoma antigens. C57BL/6J mice infected with T. crassiceps (A, B, E, F) or M. corti (C, D, G, H) (n = 7), are given here as an example. The sera of mice infected with tapeworms contained high levels of specific IgM (A, C) and IgG (B, D) raised against the antigens of the respective tapeworm, while they did not contain any significant amount of IgM (E, G) or IgG (F, H) specific to MelH. The cut-off values were determined according to Frey et al. (29).

Figure 6

Host immune response in the peritoneal cavity of mice. (A) Total numbers of leukocytes. Dots represent data from individual mice (n = 7); group medians are shown. (B) Heat maps showing the frequency of major leukocyte populations. (C, D) Total cell counts of major myeloid (C) and lymphoid (D) populations. Medians are shown; error bars are omitted to keep legibility. CD19+, B cells; CD4+, T helper cells; CD8+, cytotoxic T cells; NK+, natural killer cells; Ly6G+, neutrophils; SiglecF+, eosinophils; CD11b+Ly6C+, monocytes; LPM, large peritoneal macrophages. One-way ANOVA with Šíďák post-hoc test was used to analyze the data. * (p ≤ 0.05), ** (p ≤ 0.01), *** (p ≤ 0.001).

Figure 7

The in vitro effect of tapeworm excretory-secretory products on B16F10 cells. Graphs (A, B) show the cytotoxic effect, where (A) shows the overall survival of cells compared to control, while (B) shows the effect on the cells’ ability to grow. Graphs (C, D) focus on their invasive attributes. The ESPs’ effect on their migration capabilities (C) and on their ability to degrade the extracellular matrix (gelatin) (D) (<3, 3-10, 10-30 and >30 denote the fractions of ESPs in kDa, VCR = vincristine). The results were analyzed with a one-way ANOVA with Dunnett’s multiple comparisons test.