Stk10 Deficiency in Mice Promotes Tumor Growth by Dysregulating the Tumor Microenvironment

SIMPLE SUMMARY: The tumor microenvironment (TME) is a highly complex biological ecosystem which plays critical roles in cancer growth, evolution, and therapeutic efficacy. Identification of novel TME modulators is helpful to find new candidate targets for diagnostics and therapeutics of malignant tumors. The object of this study was to evaluate the role of serine-threonine kinase 10 (STK10) in the TME and host anti-tumor response. Our data indicate that the expression of STK10 is significantly positively associated with tumor-infiltrated immune cells. Further in vivo data revealed that Stk10 participates in anti-tumor response by regulating the activated tumor-infiltrated CTLs and tumor angiogenesis. Collectively, this is the first attempt to evaluate the correlation between STK10 and host anti-tumor response. Our data provide us with the possibility of using STK10 as a candidate target for anti-tumor immunotherapy. ABSTRACT: Serine-threonine kinase 10 (STK10) is a member of the STE20/p21-activated kinase (PAK) family and is predominantly expressed in immune organs. Our previous reports suggested that STK10 participates in the growth and metastasis of prostate cancer via in vitro and in vivo data. However, the correlation between STK10 and the tumor microenvironment (TME) remains unclear. In this study, we assessed the relationship between STK10 and the immune cells in the tumor microenvironment of prostate cancer through bioinformatic analysis, and investigated the role of Stk10 in tumor growth using an Stk10 knockout mouse model. The results showed that STK10 is significantly associated with the tumor-infiltrating immune cells including lymphocytes, neutrophils, macrophages and dendritic cells. The target deletion of host Stk10 results in increased tumor growth, due to decreased activated/effector cytotoxic T lymphocytes (CTLs) and increased vessel density in the TME. In conclusion, we demonstrate that host Stk10 is involved in the host anti-tumor response by modulating the activated tumor-infiltrated CTLs and angiogenesis.