CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers

Background: Cyclin-Dependent Kinase 16 (CDK16) plays significant biological roles in various diseases. Nonetheless, its function in different cancer types and its relationship with the Tumor Immune Microenvironment (TIME) are still not well -understood. Methods: We analyzed the expression profile, genetic alterations, clinical features, and prognostic value of CDK16 in pan -cancer using data from The Cancer Genome Atlas, Genotype -Tissue Expression databases, and in vitro experiments. Additionally, the TIMER2 and ImmuCellAI databases were utilized to assess the correlation between CDK16 expression and immune cell infiltration levels. Finally, we examined the correlation between CDK16 and the response to immunotherapy using collected immunotherapy data. Results: CDK16 is notably overexpressed in pan -cancer and is a risk factor for poor prognosis in various cancers. Our findings reveal that CDK16 regulates not only cell cycle -related functions to promote cell proliferation but also the autoimmunity-related functions of the innate and adaptive immune systems, along with other immune -related signaling pathways. Moreover, CDK16 overexpression contributes to an immunosuppressive tumor microenvironment, extensively suppressing immune -related features such as the expression of immunerelated genes and pathways, as well as the count of immune -infiltrating cells. Our analysis indicated that individuals with low CDK16 expression showed higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high CDK16 expression. Conclusions: This study establishes CDK16 as a potential biomarker for predicting poor prognosis in a wide range of cancers. Its role in shaping the immunosuppressive tumor microenvironment and influencing the efficacy of immunotherapy highlights the urgent need for developing targeted therapies against CDK16, offering new avenues for cancer treatment and management.