MedicalResearch.com Interview with:
Dr. Shuang George Zhao, MD
House Officer, Radiation Oncology
Ann Arbor, MI 48109
MedicalResearch.com: What is the background for this study?
Response: Targeting cancer through the immune system has been a longstanding goal of cancer research, and with recent advances in immunotherapy, it is now a reality. However, the role of immunotherapy in prostate cancer is still being defined. Sipuleucel-T was the first FDA approved immunotherapy in prostate cancer, and is a personalized cellular therapy that has been shown to prolong survival in patients with metastatic prostate cancer. On the other hand, two recent phase III randomized trials looking at ipilimumab, a CTLA-4 checkpoint inhibitor in metastatic prostate cancer have both been negative for their primary endpoint of OS. Interestingly, there was a PSA response, suggesting that there may be some therapeutic effect in a subset of patients. Therefore, understanding the immune infiltrate is likely critical to selecting patients and therapeutic strategies utilizing the immune system. Unfortunately, it is difficult and laborious to histologically assess immune infiltrate directly. Therefore, we used existing high throughput transcriptomic data with new computational methods in order to more fully characterize the immune landscape of localized prostate cancer.
MedicalResearch.com: What are the main findings?
Response: We analyzed gene expression data from 9393 prostate cancer samples on a commercial clinical platform. We found that computationally estimated immune content appeared to predict recurrence, metastasis, and survival. When we examined computationally estimated individual cell types, we found that certain cell types such as mast cells, natural killer cells, and dendritic cells were associated with improved prognosis and other cell types such as macrophages and T-cells were associated with worse prognosis. We also found that immune content may predict response to post-operative radiation therapy, suggesting a possible interaction. Finally, many checkpoint inhibitors target the PD-1/PD-L1 axis. However, PD-L1 is not widely expressed in prostate cancer. Interestingly, PD-L2 which also interacts with PD-1 in a similar manner is much more highly expressed in our samples, and also confers a worse prognosis suggesting that it may be a novel therapeutic target in prostate cancer.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: There may be a subset of patients with higher immune infiltrate in prostate cancer, but the role of the immune system in prostate cancer is complex with different immune cell types likely interacting with the tumor in different ways. Therefore, expanding our understanding of the underlying biology is important to make further advances in the treatment of prostate cancer.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The ongoing studies of combinations of immunotherapy and radiation in prostate cancer hold particular promise, and we believe our results support the further investigation of combining these two modalities. Additional investigation into PD-L2 as a potential therapeutic target, which is much less well studied than PD-L1, is also warranted by our findings.
Disclosures: I have received travel expenses from GenomeDx Biosciences, and have patents pending with them as wel
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ASTRO 2017 abstract:
Novel Associations Between the Immune Landscape of Prostate Cancer and Postoperative Radiation Response
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