Pei Zhang1, Xiaoming Lu1, Kaixiong Tao1, Liang Shi2, Wei Li1, Guobin Wang1, Ke Wu3. 1. Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 3. Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wuke19870625@gmail.com.
Abstract
BACKGROUND: The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in human hepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study. METHODS: Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed. RESULTS: Siglec-10 was expressed most on NK cells in HCC (40.7 ± 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 ± 1.7% versus 40.7 ± 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10(+)CD56(+) NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10(-)CD56(+) NK cells. Moreover, the number of CD24(+)CD45(-) cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 ± 0.9% versus 3.1 ± 0.9%, n = 15, P < 0.05). CONCLUSIONS: These findings suggest that Siglec-10 is associated with decreased survival and impaired NK cell function in human HCC. This process may function via the CD24-Siglec-10 interaction, which may represent a therapeutic target in HCC patients.
BACKGROUND: The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in humanhepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study. METHODS: Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed. RESULTS:Siglec-10 was expressed most on NK cells in HCC (40.7 ± 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 ± 1.7% versus 40.7 ± 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10(+)CD56(+) NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10(-)CD56(+) NK cells. Moreover, the number of CD24(+)CD45(-) cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 ± 0.9% versus 3.1 ± 0.9%, n = 15, P < 0.05). CONCLUSIONS: These findings suggest that Siglec-10 is associated with decreased survival and impaired NK cell function in human HCC. This process may function via the CD24-Siglec-10 interaction, which may represent a therapeutic target in HCC patients.
Authors: Rosa Ester Forgione; Cristina Di Carluccio; Juan Guzmán-Caldentey; Rosa Gaglione; Filomena Battista; Fabrizio Chiodo; Yoshiyuki Manabe; Angela Arciello; Pompea Del Vecchio; Koichi Fukase; Antonio Molinaro; Sonsoles Martín-Santamaría; Paul R Crocker; Roberta Marchetti; Alba Silipo Journal: iScience Date: 2020-06-02