Effector and Regulatory CD4+ T helper lineages in cancer

Abstract

Regulatory CD4+T-cells have been recently classified as regulatory T helper (Th)-like cells according to the expression of specific transcription factors, cytokines and chemokine receptors that mirror effector Th lineages. In our report: "An Atlas of Human Regulatory T Helper-like Cells Reveals Features of Th2-like Tregs that Support a Tumorigenic Environment" we found that Th2-like Tregs were increased in the tumour microenvironment in comparison with Th1-like, Th17-like and Th1/Th17-like Tregs. In addition, despite similar expression of CCR4 between all Tregs subtypes, Th2-like Tregs migrated more toward CCL17 and CCL22, and expressed higher levels of CCR8 than the other Th-like Tregs. Other studies have characterised human tissue-infiltrating Tregs and demonstrated that CCR8 is the main chemokine receptor differentially expressed in Tregs isolated from malignant tissues in comparison with healthy tissues. Given that CCR8 is a marker of Th2 lineages it is possible that Th2-like Tregs and CCR8+ Tregs are the same population of cells involved in tumour progression. However, whether they are recruited or differentiated in situ by the tumour microenvironment is still unknown. In this mini review, we describe the role of the different Th subsets in health and cancer and we present the different hypotheses about the presence of Th2-like Tregs in the tumorigenic environments.