Abstract
Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings.
Highlights
Prostate cancer is the most common cancer to be diagnosed among men in the USA [1].Radical prostatectomy and radiation therapy are the standard primary treatments for patients with early-stage prostate cancer, while androgen-deprivation therapy is the main therapy for recurrent disease and/or advanced-stage prostate cancer
Our previous study showed that high-dose Radiation therapy (RT) (25 Gy) delayed the growth of TRAMPC1 prostate tumors by approximately 1 week compared with control tumors [30]
It did not lead to tumor shrinkage. These findings indicated that TRAMP-C1 tumors were resistant to radiotherapy
Summary
Prostate cancer is the most common cancer to be diagnosed among men in the USA [1]. Radical prostatectomy and radiation therapy are the standard primary treatments for patients with early-stage prostate cancer, while androgen-deprivation therapy is the main therapy for recurrent disease and/or advanced-stage prostate cancer. Despite the advance in therapeutic treatment, prostate cancer remains the second leading cause of cancer-related death in American men because most patients progress to metastatic castration-resistant prostate cancer [2,3]. The development of effective therapy is still the main subject for prostate cancer therapy. Prostate cancer presents an immunosuppressive microenvironment, including lack of CD8+ lymphocytes’ infiltration, downregulation of major histocompatibility complex (MHC) expression, and higher expression of programmed cell death-ligand 1 (PD-L1) [4,5,6]. Turning from “cold” tumors into “hot” tumors may be a potential strategy to enhance immune response of prostate cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
