Details

Autor(en) / Beteiligte

• Chakraborty, Sreeparna
• Bhattacharjee, Pushpak
• Panda, Abir K
• Kajal, Kirti
• Bose, Sayantan
• Sa, Gaurisankar

Titel

Providence of the CD25+KIR+CD127−FOXP3−CD8+ T‐cell subset determines the dynamics of tumor immune surveillance

Ist Teil von

• Immunology and cell biology, 2018-11, Vol.96 (10), p.1035-1048

Ort / Verlag

United States: Blackwell Science Ltd

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• CD8+ T‐regulatory (Treg) cells are emerging as crucial components of immune system. Previous studies have reported the presence of FOXP3+CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of the immunosuppressive cytokines, IL10 and TGFβ. At an early stage of tumor development, we have identified a subset of FOXP3−CD8+CD25+KIR+CD127− Treg‐like cells, which are IFNγ+. However, this early‐induced CD8+CD25+CD127− T‐cell subset is certainly distinct from the IFNγ+CD8+ T‐effector cells. These CD8+CD25+CD127− T cells express other FOXP3−CD8+ Treg cell signature markers, and can selectively suppress autoreactive HLA‐E+ TFH cells as well as tumor‐induced CD4+ Treg cells. In contrast to FOXP3+CD8+ Tregs, this subset does not inhibit effector T‐cell proliferation or their functions as they are HLA‐E−. Adoptive transfer of this early‐CD8+ Treg‐like subset restrained tumor growth and inhibited CD4+ Treg generation that impedes the immune surveillance and impairs cancer immunotherapy. At the late stage of tumor development, when CD4+ Treg cells dominate the tumor‐microenvironment, CD4+ Tregs mediate the clonal deletion of these tumor‐suppressive FOXP3−IFNγ+CD8+CD25+CD127− T cells and ensure tumor immune evasion. Our findings suggest that at an early stage of the tumor, this tumor‐induced IFNγ‐producing FOXP3−CD8+CD25+CD127− T‐cell subset can potentiate immune surveillance by targeting HLA‐E‐restricted CD4+ Treg cells while leaving the effector T‐cell population unaffected. Hence, manipulating their profile can open up a new avenue in cancer immunotherapy. In this study, a FOXP3−CD8+CD25+KIR+CD127− Treg‐like subset has been identified. This subset predominated at the early stage of the tumor and suppressed HLA‐E+ TFH cells. With the progression of the tumor, CD4+ Treg cells increase in number and selectively kill these IFN‐γ producing CD8+CD25+CD127− Treg‐like cells.