Sialic acid binding Ig-like lectin 10(Siglec10)is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells.Here,by analyzing public...Sialic acid binding Ig-like lectin 10(Siglec10)is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells.Here,by analyzing public databases containing 64517 patients of 33 cancer types,we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types.In particular,Siglec10 was upregulated in patients with kidney renal clear cell carcinoma(KIRC)and was inversely associated with the prognosis of the patients.In 131 KIRC patients of our settings,Siglec10 was elevated in the tumor tissues of 83(63.4%)patients compared with that in their counterpart normal kidney tissues.Moreover,higher level of Siglec10 was associated with advanced disease(stages III and IV)and worse prognosis.Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells.In addition,luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1,which were identified by data mining.These results demonstrate that Siglec10 may have important oncogenic functions in KIRC,and represents a novel target for the development of immunotherapies.展开更多
基金supported by the National Key Research and Development Program of China(No.2020YFA0803300)the CAMS Initiative of Innovative Medicine(2021-1-I2M-014)+3 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-RC310-003 and 2020-RC310-002)the Key Project of the National Natural Science Foundation of China(No.81830093)the National Natural Science Funds for Distinguished Young Scholar(No.81425025)the National Natural Science Foundation of China(Nos.81672765,81802796,and 82073092).
文摘Sialic acid binding Ig-like lectin 10(Siglec10)is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells.Here,by analyzing public databases containing 64517 patients of 33 cancer types,we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types.In particular,Siglec10 was upregulated in patients with kidney renal clear cell carcinoma(KIRC)and was inversely associated with the prognosis of the patients.In 131 KIRC patients of our settings,Siglec10 was elevated in the tumor tissues of 83(63.4%)patients compared with that in their counterpart normal kidney tissues.Moreover,higher level of Siglec10 was associated with advanced disease(stages III and IV)and worse prognosis.Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells.In addition,luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1,which were identified by data mining.These results demonstrate that Siglec10 may have important oncogenic functions in KIRC,and represents a novel target for the development of immunotherapies.
