Thursday, May 19, 2016

Foxp3+ Tregs go against tumor in the "dark"

This week PNAS published follow-up study from Harvey Cantor's lab examining role of Helios (the Sun in Greek mythology) in Foxp3+ TREG stability. In this new study they showed that antibody [anti-GITR]-mediated down-regulation of Helios in Foxp3+ TREG causes them to acquire effector function and participate in anti-tumor response.

I will highlight relevant findings. The first finding was that mice with Helios-deficient Foxp3+ TREG showed additional resistance to tumor (however, please note that tumor growth pattern and mice survival do not correlate in Heliosfl/fl.FoxP3-Cre mice).

Similar tumor growth retardation was observed in adoptive co-transfer experiment with WT T cells and Helios-KO Foxp3+ TREG.

Mechanistically, Heliosfl/fl.FoxP3-cre TREG up-regulated effector cytokines specifically at tumor site.

Finally, treatment of mice with antibody, DTA-1, directed to GITR (glucocorticoid induced TNF receptor), caused Helios down-regulation in FoxP3+ TREG and improved tumor protection.

In summary, the authors proposed that therapeutic targeting of Helios expression in tumor-associated FoxP3+ TREG could convert them from tolerogenic cells into anti-cancer fighting cells (however, please note the authors did not formally test whether anti-cancer effect of anti-GITR antibody was indeed mediated via its effect on Helios in FoxP3+ TREG).

David Usharauli

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