Liposome promotion of tumor growth is associated with angiogenesis and inhibition of antitumor immune responses
Menée à l'aide d'un modèle murin, cette étude met en évidence des mécanismes par lesquels, en augmentant l'angiogenèse tumorale et en inhibant l'immunité antitumorale, des nanoparticules sous forme de liposomes contenant des molécules cytotoxiques sont paradoxalement susceptibles de favoriser la croissance tumorale
Liposomes have tremendous potential as drug carriers in the treatment of cancer. However, despite enhanced tumor drug delivery and decreased toxicity, patient survival rates have not improved significantly compared to corresponding free drug treatments. Importantly, we found that a liposomal nanoparticle currently used as a drug carrier in cancer patients enhanced tumor growth in an immune competent murine model of cancer. This was associated with increased tumor angiogenesis and suppression of antitumor immune responses as indicated by decreased cytokine production by tumor macrophages and cytotoxic T cells, diminished tumor infiltration of tumor-specific T cells, and decreased number of dendritic cells in tumor draining lymph nodes. These results suggest that carrier-induced immunosuppression and angiogenesis have the potential to reduce the antitumor effects of drugs loaded within. These findings may have significant implications for the current use and future development of anticancer nanoparticles and further investigations are urgently needed. We found that a liposomal drug carrier currently used in cancer patients enhanced tumor growth in an immune competent murine model of cancer. This was associated with increased tumor angiogenesis and suppression of antitumor immunity. Importantly, if these effects are operative in humans, this may partially explain why there has been an insufficient improvement in anticancer efficacy despite the major pharmacologic advantages of liposomal drugs over free drugs.
http://linkinghub.elsevier.com/retrieve/pii/S154996341400433X?showall=true