MENUImmune response prognostic for prostate cancer survival, recurrence and response to radiation therapy
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Findings indicate new avenue for personalized medicine and potentially inform use of immunotherapy treatments currently on the market for localized prostate cancer
SAN DIEGO, CA -- A new study finds that immune response in prostate cancer may be able to forecast how patients will respond to radiation therapy, as well as their likelihood of disease recurrence and survival outcomes. The analysis of more than 9,000 prostate tumors also found evidence that PD-L2, not PD-L1, may provide a key route for targeted therapies, such as immunotherapy, to slow disease progression.
"When the immune system responds to tumors, it sends specific types of immune cells directly to the tumor. Understanding this infiltration of immune cells allows researchers and oncologists to devise treatment strategies based on each patient's specific immune response and disease biology. Checkpoint inhibitors and other immunotherapies have been utilized to manage other solid tumors. Our work suggests that there may be a role for these innovative treatments in prostate cancer, as well," said Shuang (George) Zhao, M.D., lead author of the study and a radiation oncology resident at the University of Michigan in Ann Arbor.
To better define the immune landscape of localized prostate cancer, researchers examined 9,393 tumor samples from men who underwent a radical prostatectomy, including 7,826 recently collected prospective tumor samples and 1,567 retrospectively obtained samples. Immune content in the tumor samples was identified using high-throughput computational analysis with specific immune-related genes. Gene expression profiling was conducted on a commercial clinical-grade platform, and gene selection was guided by the published literature.
Clustering analysis of the 9,393 tissue samples identified a subset of patients with higher expression of immune-related pathways. This immune content score, which was predicted computationally, appeared to predict prostate cancer recurrence, metastasis and survival. Higher levels of the immune content score were associated with lower likelihood of survival, including freedom from disease progression (Hazard Ratio (HR) = 1.3, p = 0.0002), freedom from distant metastases (HR = 1.3, p = 0.0006), prostate cancer-specific survival (HR = 1.5, p = 0.0003) and overall survival (HR = 1.3, p = 0.006). Clinical outcomes were available for retrospective data only.
The immune content score also predicted response to radiation therapy following radical prostatectomy. On multivariate analysis, it interacted significantly (p = 0.017) with response to post-operative radiation therapy (PORT).
"Our analyses also found a potential interaction between immune content and radiation response, suggesting that combinations of radiation therapy and immunotherapies may be a treatment option worthy of further investigation," said Dr. Zhao.
Different types of immune cells were influential in different ways, indicating a complex interaction between immune cells and tumor cells. Specifically, higher levels of active macrophages and T-cells were prognostic for worse distant metastasis-free survival (p < 0.05), while active mast cells, NK cells and dendritic cells were associated with improved distant metastasis-free survival (p < 0.05). Individual cell types were examined from the genome-wide expression data using the CIBERSORT algorithm.
PD-L1, the target of several FDA-approved checkpoint inhibitors, was not associated with outcomes in this study, but PD-L2, which interacts with PD-1 similarly to PD-L1, was associated with worse treatment outcomes. Specifically, higher levels of PD-L2 were associated with greater likelihood for disease recurrence (HR = 1.17, p = 0.013), distant metastasis (HR = 1.25, p = 0.014) and prostate cancer death (HR = 1.45, p = 0.003).
"As immune checkpoint blockers have come to market, PD-L1 has received a great deal of attention -- but it does not appear to be widely expressed in prostate cancer. PD-L2, however, was much more highly expressed in these tumor samples, and it also was associated with worse outcomes. The understudied PD-L2 ligand may be the better therapeutic target for patients with localized prostate cancer," said Dr. Zhao.
"The immune landscape of prostate cancer is highly complex. We need to develop treatment approaches that account for individual tumor and patient characteristics in order to prescribe the best treatments for each individual prostate cancer patient."
The abstract, "Novel associations between the immune landscape of prostate cancer and post-operative radiation response," was presented in detail during a news briefing and the clinical trials session at ASTRO’s 59th Annual Meeting in San Diego.
Resources on Prostate Cancer and Radiation Therapy
- Videos: Radiation Therapy for Prostate Cancer (Spanish version), An Introduction to Radiation Therapy (Spanish version)
- Additional brochures, videos and information on radiation therapy from ASTRO’s patient site, RTAnswers.org.
- ASTRO’s clinical practice statements and guidelines
ABOUT ASTRO’S ANNUAL MEETING
ASTRO’s 59th Annual Meeting, the world’s largest scientific meeting in radiation oncology, will be held September 24-27, 2017, at the San Diego Convention Center. The 2017 Annual Meeting is expected to attract more than 11,000 attendees from across the globe, including oncologists from all disciplines and members of the entire radiation oncology team. More than 2,800 abstracts sharing results from clinical trials and other research studies will be presented in conjunction with educational sessions and keynote addresses that underscore the meeting’s theme, "“The Healing Art and Science of Radiation Oncology." Led by ASTRO President Brian Kavanagh, MD, MPH, FASTRO, the 2017 meeting will feature keynote addresses from Richard D. Zane, MD, FAAEM, Chief Innovation Officer for the University of Colorado Health System; Lucy Kalanithi, MD, FACP, widow of Paul Kalanithi, MD, the best-selling author of “When Breath Becomes Air,” with Heather Wakelee, MD, Paul’s oncologist; and Vinay K. Prasad, MD, MPH, an assistant professor of medicine at the Oregon Health & Science University. During the four-day meeting, more than 200 exhibitors will demonstrate cutting-edge technology and medical device innovations for radiation oncology. Visit us online for more information about ASTRO’s 59th Annual Meeting or press opportunities at the meeting.
ABOUT ASTRO
The American Society for Radiation Oncology (ASTRO) is the world’s largest radiation oncology society, with more than 10,000 members who are physicians, nurses, biologists, physicists, radiation therapists, dosimetrists and other health care professionals who specialize in treating patients with radiation therapies. The Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology • Biology • Physics (www.redjournal.org), Practical Radiation Oncology (www.practicalradonc.org) and Advances in Radiation Oncology (www.advancesradonc.org); developed and maintains an extensive patient website, RT Answers (www.rtanswers.org); and created the Radiation Oncology Institute (www.roinstitute.org), a nonprofit foundation to support research and education efforts around the world that enhance and confirm the critical role of radiation therapy in improving cancer treatment. To learn more about ASTRO, visit www.astro.org and follow us on our blog, Facebook and Twitter.