A dendritic cell-like transition of T cells is associated with spontaneous remission of adult T-cell leukemia-lymphoma.

Spontaneous remission in patients with various cancers has been reported. Some patients with adult T-cell leukemia-lymphoma (ATL), have experienced spontaneous remission, although mechanisms for this remain unknown. In this study, we analyzed ATL cells and human T-cell leukemia virus type 1 (HTLV-1) infected cells using Cytometry by Time-Of-Flight mass spectrometry (CyTOF). We observed a small number (less than 5% on average) of ATL cells and HTLV-1 infected cells expressed CD14 and other dendritic cell (DC) associated molecules such as CD1c, CD11b, CD11c, and CD141. Single cell analysis revealed that these T cells expressing DC markers also contained rearranged TCR genes, indicating that these cells are indeed derived from T cells. In an ATL patient who entered into remission after contracting coronavirus disease 2019 (COVID-19), the number of DC-like T cells increased, and ELISPOT assay detected CTLs against Tax in accordance with regression of ATL. These findings suggest that DC-like ATL cells acquire antigen-presenting capability, and induce spontaneous remission through enhanced immunity to the virus. Specifically, in an ATL cell line, enforced expression of IRF8 and PU.1 in addition to endogenous BATF3 expression increased CD86 expression and enabled the cells to present Tax peptide antigens to T cells. Collectively, these data indicate that ATL cells acquire antigen-presenting activity when IRF8, PU.1 and BATF3 are expressed, suggesting that transition of a subset of T cells to DC-like T cells can induce immune responses to viral antigens, resulting in spontaneous remission. Thus, the transition of T cells to DC-like T cells is a unique mechanism for spontaneous remission in ATL.