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

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-γ (IFN-γ) 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.

Drivers of heterogeneity in the glioblastoma immune microenvironment.

Glioblastoma is the most common and aggressive primary brain tumor, characterized by a highly complex and heterogeneous tumor immune microenvironment (TIME). In this review, we discuss the impact of tumor-intrinsic and tumor-extrinsic drivers that contribute to heterogeneity in the adult glioblastoma TIME, focusing on four main factors: genetic drivers, sex, age, and standard of care therapy. We describe recent insights into how each of these factors affects key aspects ranging from TIME composition to therapy response, with an emphasis on the cross-talk between tumor and immune cells. Deciphering these local interactions is fundamental to understanding therapy resistance and identifying novel immunomodulatory strategies.