Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

Abstract

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasitederived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4 1 and CD8 1T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c 1 His48 2 MHC II 1 cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti-T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth.

Parasite Infection, Carcinogenesis and Human Malignancy

“…Immunization with T. cruzi epimastigote lysate strongly inhibited tumor development in vivo by inducing the activation of both CD4(+) and CD8(+) T cells as well as by increasing numbers of CD11b/c(+) His48(−) MHC II(+) cells, which correspond to macrophages and/or dendritic cells. Antibodies against T. cruzi lysate recognized various rat and human tumor cell types such as colon and human breast cancer cells and thus mediate tumor cell killing through antibody-dependent cellular cytotoxicity (ADCC) (Ubillos et al, 2016). To illustrate this mechanism, studies have identified a parasite chaperone molecule, the T. cruzi calreticulin (TcCRT) (Aguillon et al, 2000) and demonstrated its potent antiangiogenic and antitumor effects both in-vitro and in-vivo .…”

Spices for Prevention and Treatment of Cancers

“…In a word, the antioxidant, anti-inflammatory, and immunomodulatory effects of spices have been confirmed in many studies [6]. Therefore, spices could be used to prevent and treat cancers, because oxidative stress [7,8,9,10,11,12], inflammatory stress [13,14] and immune response [15,16] have been associated with the genesis, growth, and metastasis of cancers [17,18,19]. In fact, epidemiological and experimental evidences have shown that certain spices might lower risks of some cancers [20,21,22,23].…”

Could cross‐immunological reactivity to Trypanosoma cruzi antigens be considered a rational strategy for designing vaccines against cancer?

“…We have read with great interest the study by Ubillos et al 1 Using in vitro and in vivo experimental approaches the authors reported very interesting results, showing that a vaccine built from Trypanosoma cruzi antigens protects against the development of chemically induced colon and mammary cancers in mice. From a theoretical point of view, to conceive their vaccine strategy the authors have appropriated a recent rational basis that attributes potential molecular homology between antigens of parasite and cancerous cells.…”