Nav: Home

Cancer's gene-determined 'immune landscape' dictates progression of prostate tumors

January 12, 2018

BOSTON - The field of immunotherapy - the harnessing of patients' own immune systems to fend off cancer - is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of patients, suggesting that as-yet unidentified variations among tumors result in distinct paths of disease progression and response to therapy.

Now, researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that genetic variations driving prostate cancer determine the composition of the immune cells that have been found to infiltrate primary prostate tumors. These immune cells, in turn, dictate tumor progression and response to treatment. The data, published in Nature Medicine, suggest that profiling patients' tumors based on this new information could lead to more successful clinical trials and tailored therapies for patients.

"We observed that specific genetic events resulted in striking differences in the composition of immune cells present in and around the tumor - results with important therapeutic implications," said senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. "Our data may be especially relevant for tailoring immunological therapies and for identifying responsive-patient population."

The third leading cause of cancer-related death in U.S. men, prostate cancer, is linked to a number of diverse genetic mutations that drive the disease. For example, the loss of the tumor suppressor gene PTEN is a frequent event in prostate cancer and is well known to promote the disease in combinations with a plethora of other mutations. Researchers also know that the tumor's microenvironment - the blood vessels, immune cells, signaling molecules and other factors that surround the tumor - plays an important role in tumor progression and response to therapy.

Pandolfi's team - including lead author, Marco Bezzi, a post-doctoral fellow in Pandolfi's lab - engineered mice models to represent four distinct known genetic variations of human prostate cancer. The models lacked either Pten alone or in combination with other genetic alterations known to drive the disease. When the team analyzed the tumors from these mice, they saw profound differences in the types and relative numbers of the immune cells that had accumulated in and around the tumor, what they call the tumors' "immune landscape".

For example, specific immune landscapes tumors from the genetic model lacking both Pten and the tumor suppressor gene called Trp53 demonstrated an increased accumulation of myeloid cells, the immune cells that mediate immunosuppression. In stark contrast, tumors from the genetic model lacking Pten and a different tumor suppressor gene called PML lacked intratumoral immune infiltration; that is, the researchers observed no immune cells at all in these tumors, which the scientists dubbed "cold," or "immune-deserts." All four mouse models analyzed presented very distinctive immune landscapes and these differences were maintained and exacerbated over time.

The research team also demonstrated that these differences in immune cell composition were directly dictated by the tumors themselves because of their genetic variations. Different tumors, they observed, secreted distinct chemical attractants, which in turn recruited - or didn't recruit, in the case of the immune-desert tumors - different immune cell types into the tumor. Pandolfi and colleagues further demonstrated that these differences hold true in human prostate cancer. Critically, the immune cells recruited to the tumors were found to be essential in supporting the growth and progression of these tumors.

"We observed that when present, these infiltrating immune cells were required for the tumor to thrive and found therapies to block their recruitment to be effective," said Bezzi. "On the other hand, the cancer genotype characterized by the so-called 'immune desert' phenotype, did not respond to such therapies. On this basis, we can predict the tumor response to immunotherapies and tailor treatment modalities to effectively impact tumors that are otherwise extremely aggressive," he said.

Thus, because immune cells interact with and also affect tumor response to therapy, these findings may be especially relevant for the development of more precise and effective combinations of immunotherapies and targeted therapies on the basis of the cancer genetic makeup.

"These profound differences in immunological landscapes among various cancer genotypes further highlight the need to thoroughly investigate and integrate genotypes and immune-phenotypes in the context of exploratory cancer treatments in both preclinical and clinical settings," said Pandolfi.
In addition to Pandolfi and Bezzi, study authors include, Nina Seitzer, Tomoki Ishikawa, Markus Reschke, Ming Chen, Guocan Wang, Caitlin Mitchell, Christopher Ng, Jesse M. Katon, Andrea Lunardi, and John G. Clohessy, of BIDMC; Sabina Signoretti of Brigham and Women's Hospital; and Jiangwen Zhang of the University of Hong Kong.

This work was funded by the National Institutes of Health (R01 CA102142 and R35 CA197529) and by a Jane Coffin Childs Postdoctoral Fellowship.

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox.

For more information, visit

Beth Israel Deaconess Medical Center

Related Prostate Cancer Articles:

ASCO and Cancer Care Ontario update guideline on radiation therapy for prostate cancer
The American Society of Clinical Oncology (ASCO) and Cancer Care Ontario today issued a joint clinical practice guideline update on brachytherapy (internal radiation) for patients with prostate cancer.
Patient prostate tissue used to create unique model of prostate cancer biology
For the first time, researchers have been able to grow, in a lab, both normal and primary cancerous prostate cells from a patient, and then implant a million of the cancer cells into a mouse to track how the tumor progresses.
Moffitt Cancer Center awarded $3.2 million grant to study bone metastasis in prostate cancer
Moffitt researchers David Basanta, Ph.D., and Conor Lynch, Ph.D., have been awarded a U01 grant to investigate prostate cancer metastasis.
New findings concerning hereditary prostate cancer
For the first time ever, researchers have differentiated the risks of developing indolent or aggressive prostate cancer in men with a family history of the disease.
Prostate cancer discovery may make it easier to kill cancer cells
A newly discovered connection between two common prostate cancer treatments may soon make prostate cancer cells easier to destroy.
New test for prostate cancer significantly improves prostate cancer screening
A study from Karolinska Institutet in Sweden shows that a new test for prostate cancer is better at detecting aggressive cancer than PSA.
The dilemma of screening for prostate cancer
Primary care providers are put in a difficult position when screening their male patients for prostate cancer -- some guidelines suggest that testing the general population lacks evidence whereas others state that it is appropriate in certain patients.
Risk factors for prostate cancer
New research suggests that age, race and family history are the biggest risk factors for a man to develop prostate cancer, although high blood pressure, high cholesterol, vitamin D deficiency, inflammation of prostate, and vasectomy also add to the risk.
Prostate cancer is 5 different diseases
Cancer Research UK scientists have for the first time identified that there are five distinct types of prostate cancer and found a way to distinguish between them, according to a landmark study published today in EBioMedicine.
UH Seidman Cancer Center performs first-ever prostate cancer treatment
The radiation oncology team at UH Seidman Cancer Center in Cleveland performed the first-ever prostate cancer treatment April 3 using a newly-approved device -- SpaceOAR which enhances the efficacy of radiation treatment by protecting organs surrounding the prostate.

Related Prostate Cancer Reading:

Prostate Cancer: A New Approach to Treatment and Healing
by Dr. Emilia A. Ripoll (Author), Mark B. Saunders (Author)

Prostate Cancer: A New Approach to Treatment and Healing gives readers new access to leading-edge medical information about prostate cancer, by making it simple and easy-to-understand. Essentially, this is a picture book for adults, written in everyday English, with lots of state-of-the-art information to support all the images, flow charts, tables, and diagrams. Each chapter has a patient story, doctor story, and interactive Toolbox section. The book also contains a Spouses Section (because no one goes through a prostate cancer diagnosis alone) and a Digging Deeper section for readers... View Details

Dr. Patrick Walsh's Guide to Surviving Prostate Cancer
by Patrick C. Walsh (Author), Janet Farrar Worthington (Author)

Each year, more than 230,000 men are diagnosed with prostate cancer, and 30 to 40 percent of patients who are diagnosed will eventually relapse. But the good news is that more men are being cured of this disease than ever before. Now in a revised third edition, this lifesaving guide by Dr. Patrick Walsh and award-winning science writer Janet Farrar Worthington offers a message of hope to every man facing this illness. Prostate cancer is a different disease in every man, which means that the right treatment varies for each man. Readers will discover their risk factors, simple changes that can... View Details

You Can Beat Prostate Cancer: And You Don't Need Surgery to Do It
by Robert J. Marckini (Author)

The task of choosing the right prostate cancer treatment is daunting. It is further complicated by conflicting information the patient receives from physicians and the Internet. This book is written by a prostate cancer survivor who now runs an international prostate cancer support group. It's about his journey and the important things he learned along the way. It is the book the author wishes had been available when he was diagnosed 6 years ago. It is intended to provide specific information for men who are at risk or have been recently diagnosed with prostate cancer. All major treatment... View Details

The Key to Prostate Cancer: 30 Experts Explain 15 Stages of Prostate Cancer
by Dr Mark Scholz (Author)

This book directs patients to understand options and educate them about treatments specific for their stage of prostate cancer.
·A short STAGING QUIZ directs patients to their correct stage and which of the seven sections of the book to read.
·The book is divided into seven sections written by experts in prostate cancer. Five of the sections cover the FIVE STAGES OF BLUE.
·The average reader will only need to read three sections: Section I, which covers PSA,Gleason score and body scans, Section VII, which covers lifestyle and general health and... View Details

Prostate and Cancer: A Family Guide to Diagnosis, Treatment, and Survival
by Sheldon Marks (Author)

Prostate cancer is one of the most common cancers affecting American men, with over 186,000 new cases diagnosed in the United States annually; 1 in 6 men will be diagnosed with prostate cancer during his lifetime. Renowned prostate cancer specialist Sheldon Marks offers the definitive guide for men concerned about or diagnosed with prostate cancer, and for their families.

Since the third edition (2003), there have been significant changes in treatment and resources. Working with Dr. Judd Moul, the Chairman of Urology at Duke and one of the world's top experts on prostate cancer, Marks... View Details

100 Questions & Answers About Prostate Cancer
by Pamela Ellsworth (Author)

100 Questions & Answers About Prostate Cancer provides authoritative and practical answers to the most common questions asked by patients and their loved ones. Providing both doctor and patient perspectives, this easy-to-read book is a comprehensive guide to the basics of prostate cancer, risk factors and prevention, diagnosis, treatment, survivorship, and life after diagnosis. Written by Dr. Pamela Ellsworth, a prominent urologist and best-selling author, Questions & Answers About Prostate Cancer is an invaluable resource for anyone interested in learning what to expect after being diagnosed... View Details

Thrive Don't Only Survive: Dr.Geo's Guide to Living Your Best Life Before & After Prostate Cancer
by Dr. Geo Espinosa (Author)

Prostate cancer is not the end—it’s the beginning. It’s the point where you start taking control.

Information on what to do isn't hard to find. There are dozens of books on prostate cancer, as well as a massive amount of online resources. What's lacking, however, is a trusted, reliable source on implementing the abundance of scientific evidence in a way that’s realistic and sustainable.

Based on his extensive research and clinical experience on natural medicine for prostate problems, Dr. Geo has created a lifestyle blueprint that men can apply immediately to thrive before or... View Details

An ABC of Prostate Cancer Today: My Journey over 4 Continents to find the BEST Cure
by Alan G Lawrenson (Author)

“An ABC of Prostate Cancer Today – 2nd Edition replaces its best- selling predecessor, “An ABC of Prostate Cancer in 2015”. The new edition provides the reader with comprehensive information on the very latest diagnosis tests that are available and now becoming routinely used in leading clinics, hospitals and specialist practice around the world. A leading urological surgeon who reviewed the book said: “All my registrars (interns) should get a copy of this book and fully digest its contents.” Another specialist said: “Every general practitioner (physician) in the country should... View Details

Prostate Cancer For Dummies
by Paul H. Lange (Author), Christine Adamec (Author)

Hearing that you have prostate cancer, or even that you may have it, is very scary. But this disease, in many cases, is curable. Even if you have advanced cancer that's spread beyond the prostate, many treatments help extend your life for years. You need good information to help you with the decisions that lie ahead, and this book provides you with this information.

Prostate Cancer For Dummies can help you if

You have prostate cancer (or you think that you have it), or someone close to you has it. You want information on treatments for prostate cancer as you form a treatment... View Details

The Definitive Guide to Prostate Cancer: Everything You Need to Know about Conventional and Integrative Therapies
by Aaron Katz (Author)

The complete guide to coping with prostate cancer, with expert health advice for every man
This comprehensive handbook gives men the vital information they need to effectively navigate every
step of dealing with prostate cancer. A newly diagnosed cancer patient faces a mind-numbing array of treatment options, including medical therapies that carry serious side effects―and determining the right course of action is an overwhelming task. In simple yet scientific terms, this book empowers readers with the tools they need to proactively fight cancer by making the most informed treatment... View Details

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

The Consequences Of Racism
What does it mean to be judged before you walk through the door? What are the consequences? This week, TED speakers delve into the ways racism impacts our lives, from education, to health, to safety. Guests include poet and writer Clint Smith, writer and activist Miriam Zoila Pérez, educator Dena Simmons, and former prosecutor Adam Foss.
Now Playing: Science for the People

#465 How The Nose Knows
We've all got a nose but how does it work? Why do we like some smells and not others, and why can we all agree that some smells are good and some smells are bad, while others are dependant on personal or cultural preferences? We speak with Asifa Majid, Professor of Language, Communication and Cultural Cognition at Radboud University, about the intersection of culture, language, and smell. And we level up on our olfactory neuroscience with University of Pennsylvania Professor Jay Gottfried.