Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model

Mechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infiltrating cells, the contribution of gal-9 produced by malignant cells has never been demonstrated in an animal model. Therefore, we derived isogenic clones—either positive or negative for gal-9—from the MB49 murine bladder carcinoma cell line. A progressive and consistent reduction of tumor growth was observed when gal-9-KO cells were subjected to serial transplantations into syngeneic mice. In contrast, tumor growth was unaffected during parallel serial transplantations into nude mice, thus linking tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. This stronger immune response was at least in part explained by changing patterns of response to interferon-γ. One consistent change was a more abundant production of CXCL10, a major inflammatory factor whose production is often induced by interferon-γ. Overall, these observations demonstrate for the first time that serial transplantation into syngeneic mice can be a valuable experimental approach for the exploration of novel mechanisms of tumor immune escape.

Matrix mediated fluorescence enhancement — why nanoparticles and PPIX make a friendly couple

The hexyl ester of 5-aminolevulinic acid (HAL) is an efficient inducer of the endogenous photosensitizer protoporphyrin IX (PPIX) in neoplastic tissue and approved for the fluorescence photodetection of bladder cancer. It is, however, limited to topical application due to unsuitable pharmacokinetic and pharmacodynamic properties following systemic administration. In this study we sought to prepare HAL laden polymeric nanoparticles made from polylactic acid (PLA) as possible means to improve the systemic bioavailability of HAL. Nanoparticles were prepared by nanoprecipitation. Particle size and morphology of freshly prepared and dehydrated nanoparticles were assessed and the ability to generate PPIX fluorescence was tested on a T24 human bladder carcinoma cell line. Fluorescence intensities of cells incubated with nanoencapsulated HAL were significantly higher than in presence of free HAL. Interestingly, the effect was — at least partly — provoked by the direct interaction of exogenously induced PPIX with the nanoparticles.