Elucidation of the Multi-step Molecular Mechanism of Carcinogenesis in Adult T-cell Leukemia/Lymphoma—Multiple Novel Therapeutic Target Candidates Identified for an Intractable Disease

Single-cell multi-omics analysis, a state-of-the-art technology, was performed using the largest number of clinical specimens for a single disease.

We investigated the pathology of viral carcinogenesis by utilizing a technology that can obtain not only comprehensive mRNA expression data from each single cell but also expression data for over 100 cell surface markers and T/B cell receptor repertoire information.

This enabled the precise identification of cells infected with human T-cell leukemia virus type 1 (HTLV-1), the causative virus of adult T-cell leukemia/lymphoma (ATL), and allowed for expression analysis in cell populations that were impossible to analyze with conventional methods.

As a result, we identified multiple new HTLV-1 infection markers and ATL progression markers, and also experimentally demonstrated that they could be novel therapeutic target candidates.

This study's comprehensive analysis revealed various phenomena, such as changes in the immune microenvironment associated with HTLV-1 infection and progression to ATL, and alterations in the microenvironment due to genetic abnormalities in tumor cells, thereby presenting new directions for future research on ATL pathology and viral carcinogenesis.