Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

Adult T-cell leukemia/lymphoma (ATL), an aggressive type of T-cell malignancy, is caused by the human T-cell leukemia virus type I (HTLV-1) infections. The outcomes, following therapeutic interventions for ATL, have not been satisfactory. Photodynamic therapy (PDT) exerts selective cytotoxic activity against malignant cells, as it is considered a minimally invasive therapeutic procedure. In PDT, photosensitizing agent administration is followed by irradiation at an absorbance wavelength of the sensitizer in the presence of oxygen, with ultimate direct tumor cell death, microvasculature injury, and induced local inflammatory reaction. This review provides an overview of the present status and state-of-the-art ATL treatments. It also focuses on the photodynamic detection (PDD) of hematopoietic malignancies and the recent progress of 5-Aminolevulinic acid (ALA)-PDT/PDD, which can efficiently induce ATL leukemic cell-specific death with minor influence on normal lymphocytes. Further consideration of the ALA-PDT/PDD system along with the circulatory system regarding the clinical application in ATL and others will be discussed. ALA-PDT/PDD can be promising as a novel treatment modality that overcomes unmet medical needs with the optimization of PDT parameters to increase the effectiveness of the tumor-killing activity and enhance the innate and adaptive anti-tumor immune responses by the optimized immunogenic cell death

Human T-Lymphotropic Virus Type 1 (HTLV-1) and Regulatory T Cells in HTLV-1-Associated Neuroinflammatory Disease

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that is the causative agent of adult T cell leukemia/lymphoma (ATL) and associated with multiorgan inflammatory disorders, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uveitis. HTLV-1-infected T cells have been hypothesized to contribute to the development of these disorders, although the precise mechanisms are not well understood. HTLV-1 primarily infects CD4+ T helper (Th) cells that play a central role in adaptive immune responses. Based on their functions, patterns of cytokine secretion, and expression of specific transcription factors and chemokine receptors, Th cells that are differentiated from naïve CD4+ T cells are classified into four major lineages: Th1, Th2, Th17, and T regulatory (Treg) cells. The CD4+CD25+CCR4+ T cell population, which consists primarily of suppressive T cell subsets, such as the Treg and Th2 subsets in healthy individuals, is the predominant viral reservoir of HTLV-1 in both ATL and HAM/TSP patients. Interestingly, CD4+CD25+CCR4+ T cells become Th1-like cells in HAM/TSP patients, as evidenced by their overproduction of IFN-γ, suggesting that HTLV-1 may intracellularly induce T cell plasticity from Treg to IFN-γ+ T cells. This review examines the recent research into the association between HTLV-1 and Treg cells that has greatly enhanced understanding of the pathogenic mechanisms underlying immune dysregulation in HTLV-1-associated neuroinflammatory disease