Eosinophils Enable the Antitumour T Cell Response

RESEARCH HIGHLIGHTS

Nature Reviews Immunology | AOP, published online 15 May 2015; doi:10.1038/nri3861

GRANULOCYTES Eosinophils enable the antitumour T cell response

Tumour-associated eosinophilia is depletion. Eosinophils sorted from macrophages by eosinophils might

frequently observed in patients with TReg cell-depleted tumours produced explain the observed vessel cancer, and eosinophils can directly large amounts of these chemokines, normalization. kill tumour cells in vitro. However, which are potent chemoattractants The restricted access of effector intratumoral eosinophils have for CD8+ T cells, leading the authors T cells into tumours is a major limita- been associated with both good to suggest that tumour-associated tion to successful immunotherapy, and bad prognoses in human eosinophils promote T cell chemo so the authors investigated whether studies, and mouse models attraction. In support of this model, eosinophils could improve the have not shown a direct effect kinetic studies of tumours showed efficacy of adoptive T cell transfer. of eosinophils on tumour growth. that eosinophil infiltration precedes The transfer of tumour-specific Instead, this study shows that infiltration of CD8+ T cells. CD8+ T cells together with acti- eosinophils are crucial accessory In addition to chemokine vated eosinophils led to greater cells in the antitumour immune production, tumour-associated inhibition of tumour growth response that enable the infiltration eosinophils were shown to promote and increased survival of of CD8+ T cells. vascular normalization of the mice compared with transfer In mice with MO4 melanoma tumour — the conversion of a small of T cells alone in two mouse tumours, the depletion of number of dilated, tortuous blood tumour models. The positive

regulatory T (TReg) cells vessels to a larger number of effect of eosinophils on tumour resulted in tumour smaller vessels — which is rejection could be prevented by rejection that was associated with decreased antibody-mediated blockade of CCL5, associated with leakiness, improved perfu- CXCL9 and CXCL10. the infiltration of sion and decreased hypoxia, The authors conclude that eosino- + S.Brad activated CD8 T cells all of which increase T cell phils, which are probably attracted br oo k and of eosinophils. infiltration and activity. to naturally occurring tumours by / N P G Eosinophil depletion Macrophages sorted from MO4 necrotic damage, have an important using a Siglec-F-specific anti- tumours after the co-transfer of role in supporting cytotoxic T cell body significantly inhibited tumour eosinophils and CD8+ T cells were infiltration. In this context, the low hi rejection after TReg cell depletion and mainly CD206 MHC class II authors note that it is of particular decreased mouse survival. This effect M1-like macrophages, compared interest that an increased number of eosinophil depletion was associ- with the CD206hiMHC class IIlow of eosinophils has been reported ated with a decreased number of M2-like macrophages found in in patients with melanoma during activated CD8+ T cells in the tumour. untreated tumours. As M2-like immunotherapy with ipilimumab. In the absence of eosinophils, macrophages produce tumour- It remains to be seen whether there was a significant impairment angiogenesis factors such as vascular these eosinophils contribute to the eosinophils of the upregulated expression of var- endothelial growth factor — the therapeutic success of this drug. could improve ious pro-inflammatory genes in the expression levels of which were Kirsty Minton tumour microenvironment induced significantly lower in macrophages the efficacy of ORIGINAL RESEARCH PAPER Carretero, R. et al. by the depletion of TReg cells. In par- from eosinophil- and T cell-treated Eosinophils orchestrate cancer rejection by adoptive T cell ticular, expression of the chemokine tumours compared with untreated normalizing tumor vessels and enhancing transfer genes encoding CCL5, CXCL9 and tumours — the authors suggest that infiltration of CD8+ T cells. Nature Immunol. http://dx.doi.org/10.1038/ni.3159 (2015) CXCL10 was reduced by eosinophil M1 skewing of tumour-associated

NATURE REVIEWS | IMMUNOLOGY VOLUME 15 | JUNE 2015