O2-8-5 - Possible stimulatory immune checkpoint molecules releasing allows adult T-cell leukemia/lymphoma development

Abstract

The interleukin (IL)-2 receptor α chain (IL-2Rα, CD25) and CD30 are cell membrane proteins expressed on activated T-cell. High levels of soluble cytokine receptors, soluble IL-2Rα (sIL-2R) and soluble CD30 (sCD30) are detected in the serum of patients with adult T-cell leukemia/lymphoma (ATL), which is a highly aggressive leukemia/lymphoma caused by human T-cell leukemia virus type 1 (HTLV-1) (Nishioka C, Takemoto S, et al. 2005; Porunkuna R, Takemoto S, et al. 2014). Freshly isolated leukemic cells from acute type ATL patients express little CD30 on the surface, and predominantly produce sCD30 (Pornkuna R, Nishioka C, and Takemoto S. 2014). We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers (Takemoto S, et al. 2015). We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sIL-2R and sCD30 concentrations at baseline were significantly higher in cases than in controls (P = 0.009 and P<0.001, respectively). In the univariate logistic regression analysis, a higher sIL-2R (≥546.5 U/mL) or sCD30 (≥30.2 U/mL) was significantly associated with ATL development. Among cases, sIL-2R and sCD30 concentrations tended to increase at the time of diagnosis of aggressive-type ATL, but the concentrations were stable in those developing the smoldering-type. High levels of sIL-2R probably down-regulate the proliferative capability of T cells that encounter tumor cells, and proliferating ATL cells are thought to release sCD30, and excess sCD30 may block CD30L on normal activated T cells and myeloid cells, protecting CD30+ ATL cells from apoptosis. Accordingly, high levels of sIL-2R and sCD30 suggest that impaired tumor surveillance leads to the survival of ATL cells. The interleukin (IL)-2 receptor α chain (IL-2Rα, CD25) and CD30 are cell membrane proteins expressed on activated T-cell. High levels of soluble cytokine receptors, soluble IL-2Rα (sIL-2R) and soluble CD30 (sCD30) are detected in the serum of patients with adult T-cell leukemia/lymphoma (ATL), which is a highly aggressive leukemia/lymphoma caused by human T-cell leukemia virus type 1 (HTLV-1) (Nishioka C, Takemoto S, et al. 2005; Porunkuna R, Takemoto S, et al. 2014). Freshly isolated leukemic cells from acute type ATL patients express little CD30 on the surface, and predominantly produce sCD30 (Pornkuna R, Nishioka C, and Takemoto S. 2014). We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers (Takemoto S, et al. 2015). We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sIL-2R and sCD30 concentrations at baseline were significantly higher in cases than in controls (P = 0.009 and P<0.001, respectively). In the univariate logistic regression analysis, a higher sIL-2R (≥546.5 U/mL) or sCD30 (≥30.2 U/mL) was significantly associated with ATL development. Among cases, sIL-2R and sCD30 concentrations tended to increase at the time of diagnosis of aggressive-type ATL, but the concentrations were stable in those developing the smoldering-type. High levels of sIL-2R probably down-regulate the proliferative capability of T cells that encounter tumor cells, and proliferating ATL cells are thought to release sCD30, and excess sCD30 may block CD30L on normal activated T cells and myeloid cells, protecting CD30+ ATL cells from apoptosis. Accordingly, high levels of sIL-2R and sCD30 suggest that impaired tumor surveillance leads to the survival of ATL cells.