4.7 Article

Trypanosoma cruzi-Derived Molecules Induce Anti-Tumour Protection by Favouring Both Innate and Adaptive Immune Responses

期刊

出版社

MDPI
DOI: 10.3390/ijms232315032

关键词

lung cancer; glycosylation; anti-tumour immune response; innate immunity; Trypanosoma cruzi

资金

  1. Agencia Nacional de Investigacion e Innovacion
  2. Comision Sectorial de Investigacion Cientifica (CSIC) [FMV 1_2017_1_136442]
  3. GSK/ANII FSGSK 1_2017_1_145466 (Uruguay)
  4. CAP (UdelaR) and PEDECIBA

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This study found that immunizations with a Trypanosoma cruzi lysate can prevent lung tumor growth and induce anti-tumor immune responses. The induced immunity and tumor protection are associated with the activation of natural killer cells, the production of interferon-gamma, and tumor cell cytotoxicity.
Lung cancer remains the leading cause of cancer mortality worldwide. Thus, the development of strategies against this type of cancer is of high value. Parasite infections can correlate with lower cancer incidence in humans and their use as vaccines has been recently explored in preclinical models. In this study, we investigated whether immunisations with a Trypanosoma cruzi lysate from epimastigotes protect from lung tumour growth in mice. We also explore the role of parasite glycans in the induction of the protective immune response. A pre-clinical murine cancer model using the lung tumour cell line LL/2 was used to evaluate the anti-tumour potential, both in preventive and therapeutic settings, of a T. cruzi epimastigote-derived protein lysate. Immunisation with the parasite lysate prevents tumour growth and induces both humoral and cellular anti-tumour immune responses to LL-2 cancer cells. The induced immunity and tumour protection were associated with the activation of natural killer (NK) cells, the production of interferon-gamma (IFN-gamma) and tumour cell cytotoxicity. We also show that mannose residues in the T. cruzi lysate induce Toll-like receptor (TLR) signalling. The evaluated T. cruzi lysate possesses anti-tumour properties likely by activating innate and adaptive immunity in a process where carbohydrates seem to be essential.

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