SAN DIEGO, Sept. 24, 2017 /PRNewswire-USNewswire/ -- 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.
Findings will be presented today at the 59th Annual Meeting of the
American Society for Radiation Oncology (ASTRO).
"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, MD, 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," will be
presented in detail during a news briefing and the clinical trials
session at ASTRO's 59th Annual Meeting in San Diego (full details below). To schedule an
interview with Dr. Zhao and/or outside experts in prostate cancer
or immunotherapy combinations, contact ASTRO's media relations team
on-site at the San Diego
Convention Center September 24 through
27, by phone at 703-286-1600 or by email at
press@astro.org.
ATTRIBUTION TO THE AMERICAN SOCIETY OF RADIATION ONCOLOGY
(ASTRO) ANNUAL MEETING REQUESTED IN ALL COVERAGE.
This news release contains additional and/or updated
information from the study author(s). Full original abstract
and author disclosures available on the final page of this
release.
Study Presentation Details
- Scientific Session: Clinical Trials, Sunday, September 24, 3:15 – 4:45 p.m. Pacific time, San Diego Convention Center, Ballroom 20
- News Briefing: Monday, September
25, 11:00 a.m. – 12:00 p.m. Pacific, San
Diego Convention Center, room 24C, webcast:
http://www.bit.do/astro17-2
Resources on Prostate Cancer and Radiation Therapy
- Digital brochure: Radiation Therapy for Prostate Cancer
(Spanish version)
- 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.
Contact: Liz
Gardner
703-286-1600
liz.gardner@astro.org
Leah Kerkman
Fogarty
703-839-7336
leah.fogarty@astro.org
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SOURCE American Society for Radiation Oncology