Th2 cells inhibit growth of colon and pancreas cancers by promoting anti-tumorigenic responses from macrophages and eosinophils

BACKGROUND: Immunotherapy of gastrointestinal cancers is challenging; however, several lines of evidence suggest that adoptive transfer of stimulated or modified immune cells supports not only a protective role of immune cells in the tumor microenvironment (TME), but actively participates in the elimination of cancer cells. METHODS: In vivo studies employing cancer cell-derived allograft murine models of gastrointestinal cancers were performed. The effects of T helper (Th) 2 cells on gastrointestinal cancer growth and TME composition using adoptive transfer of Th2 cells, interleukin (IL)-5 treatment, and immunofluorescence, multiplex and real-time PCR were explored. RESULTS: Th2 cells play an essential role in the inhibition of colon and pancreas cancer progression. In murine models using adoptive transfer of Th2 cells, Th2 cells were responsible for generation of apoptotic factors and affected macrophage as well as eosinophil recruitment into tumors where they produced cytotoxic factors. Th2 cells led to IL-5 hypersecretion, linking Th2 cell and eosinophil anti-tumorigenic function. Recombinant IL-5 administration was also related to inhibition of gastrointestinal tumor growth. Both Th2 cells and eosinophils directly killed gastrointestinal cancer cells in vivo. CONCLUSIONS: Th2 cells, eosinophils and IL-5 are significant in inhibiting gastrointestinal tumor growth, pointing toward TME reprogramming as a Th2 cell-mediated anti-tumorigenic mechanism of action.

Damian Jacek, Ioannis Karagiannidis, Ellen J. Beswick