by ecancer reporter Janet Fricker

Eosinophils support tumour rejection when ‘stringent’ requirements are fulfilled, concludes a German study published in Nature Immunology.

Eosinophils are types of white blood cells containing coarse granules that are known to express large numbers of different cell-surface receptors, including adhesion molecules.

Eosinophils are thought to play a role in tissue repair and homeostasis, and to participate in immune responses, such as clearance of parasites and regulation of diseases, including allergic asthma and autoimmune disorders.

Several studies have suggested that eosinophils are attracted to tumours by chemotatic factors.

Other studies have shown the presence of eosinophils in tumours to be associated with good prognosis.

But it remains uncertain if eosinophils are essential for tumour rejection or are mere ‘bystander cells’.

In the current study, Günter Hämmerling and colleagues, from the German Cancer Research Centre in Heidelberg, used a mouse model to explore whether eosinophils might serve as ‘accessory’ cells contributing to tumour-specific T cell responses.

The team showed that the transfer of activated T cells into wild-type mice bearing large established tumours resulted in only mild inhibition of  tumour growth; while transfer of T cells together with activated eosinophils led to much greater inhibition of tumour growth and significantly extended mouse survival.

Furthermore, the transfer of T cells together with eosinophils that had not been activated failed to inhibit tumour growth, demonstrating that eosinophils need to be activated to exert their anti-tumour activity.

Invivo blockade of the chemokines CCL5, CXCL9 and CXCL10 by injection of a ‘cocktail’ of antibodies to these chemoattractants impaired tumour rejection obtained by the combination of eosinophils plus T cells.

Furthermore, activated eosinophils initiated substantial changes in the tumour microenvironment, including macrophage polarisation and normalisation of the tumour vasculature, both known to promote tumour rejection.

“Our results help to explain some of the discrepancies in the literature on tumour-associated eosinophilia in patients with cancer and establish the conditions under which eosinophils are able to support tumour immunity,” write the authors.

“The mere presence of eosinophils cannot be used as a prognostic factor in clinical studies without determination of the precise activation and polarisation status of eosinophils, as well as the status of T cell infiltration,” they add.

“On the basis of our study, and owing to their tumour-homing properties, eosinophils might now emerge as a promising tool for the improvement of clinical cancer immunotherapy,” they write.

Reference

R Carretero, I Sektioglu, N Garbi, et al. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8 T cells. Nature Immunology.