Expanded subpopulation of FoxP3⁺ T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs

Conversion of conventional T cells into T regulatory cells (Tregs) has been proposed as a potential mechanism for Treg expansion in cancer. However, this evidence is supported by in vitro or mouse model studies with no data from in vivo or human studies to support its role in enriching peripheral and tumor-infiltrating Tregs. Recent work has shown that induced FoxP3⁺ Tregs (iTregs) do not express Helios; an Ikaros family transcription factor. We analyzed peripheral blood samples from untreated renal cell carcinoma (RCC) patients and following interleukin (IL)-2 treatment for the expression of FoxP3 and Helios. Our work shows that expanded peripheral FoxP3⁺ Tregs in untreated RCC patients co-express Helios. Interestingly, IL-2 administration results in expansion of FoxP3⁺Helios⁺ natural Tregs (nTregs) significantly more than FoxP3⁺Helios^- iTregs. Our work shows that the increased FoxP3⁺ Treg subpopulation in RCC patients co-express Helios, indicating that they could be derived from natural but not induced Tregs.