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 the 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. We observed a small number (less than 5% on average) of ATL cells and HTLV-1–infected cells that 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 T-cell receptor genes, indicating that these cells are indeed derived from T cells. In a patient with ATL who entered remission after contracting coronavirus disease 2019, the number of DC-like T cells increased, and an enzyme-linked immunosorbent spot assay detected CTLs against the Tax protein in accordance with a 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 the 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. Overall design: Peripheral blood mononuclear cells (PBMCs) from adult T-cell leukemia/lymphoma (ATL) patients were processed for single-cell RNA sequencing (scRNA-seq) using the 10X Genomics Chromium Next GEM Single Cell 5' Reagent Kit v2 (Dual Index) according to the manufacturer's instruction. Briefly, a single-cell suspension was loaded onto the Chromium Next GEM Chip K for GEM generation. Following GEM formation, gel beads were dissolved, and co-partitioned cells were lysed. The transcripts present in the beads were barcoded and reverse-transcribed into full-length cDNA. The resulting cDNA was amplified via PCR, and then used to generate the 5' gene expression and T-cell receptor (TCR) V(D)J libraries according to the manufacturer's protocol. Finally, sequencing was performed on the DNBSEQ-G400RS platform.