Foxp3+ Tregs depletion activates anti-cancer immunity via eosinophils

Eosinophils are usually associated with atopic/allergic conditions. However, as with all cells involved in type II immune response, eosinophil's role in host's defense is not entirely clear.

This new paper in Nature Immunology provided evidence for eosinophil's anti-tumor function. The paper itself is quite "primitive", observation-type of research article. It belongs more to JEM, if you ask me. Still, it was accepted within 1 month of its submission to Nature Immunology. 

It appears that initial focus of this research was Foxp3+ Tregs. The authors showed that Foxp3⁺ Tregs depletion in Foxp3.LuciDTR-4 mice induced B16 melanoma rejection expressing nominal OVA antigen (MO4 tumor cells).

Surprisingly, this rejection of MO4 tumor was accompanied with selective eosinophil infiltration at tumor site.

Indeed, concomitant depletion of eosinphils with Siglec-F antibody significantly reduced anti-cancer effect seen with Foxp3⁺ Tregs depletion.

Additional experiments showed that anti-tumor effectiveness of adoptively transferred OVA-specific CD8 T cells were eosinophil dependent, though only in vitro IFN-γ + TNF-α activated, but not resting eosinophils could provide such help to CD8 T cells. Eosinophils alone were not effective.

The authors went on to show that activated eosinophils attracted CD8 T cells to tumor site and promoted normalization of tumor vasculature.

In summary, these results suggests that depletion of Foxp3⁺ Tregs activates eosinophils which in turn recruit CD8 T cells into tumor site leading to anti-tumor effect.

Now, why are eosinophils specifically involved in tumor protection in this model is not clear. What attracts eosinophils into tumors?

David Usharauli