IMPACTS OF TUMOR-INTRINSIC STING AND TUMOR-DERIVED IFN-β ON CANCER IMMUNOTHERAPY

Abstract

Despite the significant progress in cancer therapy, immunosuppressive microenvironments and metastatic tumors continue to pose a significant challenge in achieving successful treatment outcomes. As a result, there is a pressing need for a systemic antitumor immune response that can precisely target distant tumors and stimulate a comprehensive, adaptive reaction across the entire body. We thoroughly evaluated the potential benefits of tumor- intrinsic STING in modulating systemic antitumor immune responses post tumor cryoablation. We included tumor cryoablation as part of our treatment plan. It can potentially create whole-cell tumor vaccines through immunogenic cell death, activating the STING pathway and stimulating an immune response against cancer cells. Based on our extensive research, we have investigated that the success of cryoablation is highly dependent on a functioning tumor cell-intrinsic STING pathway. Our study has shown that effective local tumor control, prevention of lung metastasis, and the abscopal effect on distant tumors all rely on a functioning tumor cell-intrinsic STING pathway after tumor cryoablation. Our findings suggest that the tumor cell-intrinsic STING pathway plays a crucial role in the success of cryoablation. Additionally, the expression of STING-related signaling components may serve as a potential biomarker for therapy response of cancer patients.

Furthermore, IFN-β can boost the immune system's ability to target cancer cells, which may result in better treatment outcomes for cancer patients. However, the role played by tumor-derived IFN-β in influencing antitumor immunity on a systemic level is not yet fully understood and requires additional research to be conducted. Thus, it is crucial to examine the effects of tumor-derived IFN-β on overall systemic antitumor immunity. Our work has revealed that IFN-β, derived from tumors, can effectively trigger an immune response against the tumor, leading to its inhibition. Additionally, our findings have demonstrated an increase in the number of functional CD8+ T cells present in the tumor microenvironment (TME). This rise in CD8+ T cells generates a much broader antitumor immunity throughout the body, ultimately rejecting tumors located far away from the primary tumor. These findings suggest that tumor-derived IFN-β can be a promising therapeutic approach for patients suffering from advanced or aggressive cancers.