Fight against cancer:

Featured here is Indra and Rani Anandasabapathy's daughter Niroshana. I am pleased to publish this on our Blog. "Cell" and "Nature" are two of the most prestigious journals in the Basic Sciences.

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• June 29, 2017

New insights into why the immune system fails to see cancer

Killer T cells surround a cancer cell. Credit: NIH

Journal reference: Cell  

Provided by: Brigham and Women's Hospital  

Cancer hides in plain sight of the immune system. The body's natural tumor surveillance programs should be able to detect and attack rogue cancer cells when they arise, and yet when cancer thrives, it does so because these defense systems have failed. A team of investigators led by Niroshana Anandasabapathy, MD, PhD, at Brigham and Women's Hospital have uncovered a critical strategy that some cancers may be using to cloak themselves - they find evidence of this genetic program across 30 human cancers of the peripheral tissue, including melanoma skin cancer. Their r"Our study reveals a new immunotherapy target and provides an evolutionary basis for why the immune system may fail to detect cancers arising in tissues," said corresponding author Anandasabapathy, of BWH's Department of Dermatology. "The genetic program we report on helps the immune system balance itself. Parts of this program prevent the immune system from destroying healthy organs or tissues, but might also leave a blind spot for detecting and fighting cancer."

The authors studied immune mononuclear phagocytes - a group of disparate cells that act as the "Pac man" of the immune system. When these cells detect foreign invaders and dying normal tissues, they devour or engulf their components. These cells then present these components on their surface teach T cells to maintain tolerance to healthy tissues, or to fight infections and pathogens. Despite differences in function, all immune mononuclear phagocytes found in the skin- (a peripheral tissue like lung and gut) share a common set of genetic programming, which is further enhanced when they enter the tissue. This program is conserved in fetal and adult development, and across species. And, the research team reports, is co-opted by multiple human cancers of tissue.esults are published June 29 in Cell.

The team finds that this program is prompted by an "instructive cue" from interferon gamma - a molecule that plays a critical role in regulating immunity. The authors find IFN-gamma for mononuclear phagocytes in development but that IFN-gamma and tissue immune signatures are much higher in skin cancer than in healthy skin. Having an immune response measured by IFN-gamma and tissue signatures correlated with improved metastatic melanoma survival outcomes, making these signatures potential biomarkers for cancer survival.

The authors reasoned such a program might contain key molecules that help the immune system reduce inflammation, but that might also leave a blind spot to cancer detection. One of the key genes the researchers detected is suppressor of cytokine signaling 2 (SOCS2). When this gene was turned off in a mouse model, the immune system was able to robustly detect and reject cancer in models of melanoma and thymoma (cancer of the thymus). They also observed improved vaccination responses, and heightened auto-inflammation suggesting this gene normally dampens auto-infla

"Our research suggests that these cancers are co-opting tissue-specific immune development to escape detection, but we see that turning off SOCS2 unmasks them," said Anandasabapathy. "This sheds new light on our understanding of how the immune system is programed to see cancers and also points the way toward new therapeutic targets for treating cancers that have these signatures."

 Explore further: Researchers identify key mutation that suppresses the immune system in melanoma

More information: Nirschl CJ et al. "IFN-gamma-dependent tissue immune homeostasis is co-opted in the tumor microenvironment" Cell DOI: 10.1016/j.cell.2017.06.01mmatory responses and contracts protective immunity.

Please also read the write up in yesterday's Sunday Times. 

Sunday Times 2

Fight against cancer: Doctor with Lankan roots leads team in research breakthrough

View(s): 253

NEW YORK – A team of investigators, led by Dr Niroshana Anandasabapathy, a physician of Sri Lankan parentage and an Assistant Professor of Dermatology at the Harvard Medical School, has discovered new insights into why the immune system fails to see cancer—even though “it hides in plain sight of the immune system”.

The body’s natural tumour surveillance programmes should be able to detect and attack rogue cancer cells when they arise, and yet when cancer thrives, it does so because these defence systems have failed, according to the study.

Described as a new frontier for cancer, and called immunotherapy, the investigators have uncovered a critical strategy that some cancers may be using to cloak themselves as they have found evidence of this genetic programme across 30 human cancers of the peripheral tissue, including melanoma skin cancer. Their results have been published in Cell, a medical research journal.

“Our study reveals a new immunotherapy target and provides an evolutionary basis for why the immune system may fail to detect cancers arising in tissues,” said Anandasabapathy. “The genetic programme we report on helps the immune system balance itself. Parts of this programme prevent the immune system from destroying healthy organs or tissues, but might also leave a blind spot for detecting and fighting cancer.”

Dr Anandasabapathy, the lead author, is an MD, Phd from the Stanford University Medical School, held a Dermatology Fellowship at the New York University Medical Center, researched in Immunology at the Rockefeller Institute and worked with the late Ralph Steinman – (who was awarded the Nobel prize for his work on the role of DENDRITIC cells in immunology).

Currently at Brigham and Women’s Hospital in Boston, Dr Anandasabapathy is the daughter of Rani and Dr Indra Anandasabapathy, an anesthesiologist in Staten Island, New York, and who graduated from the Medical School in Colombo in 1967.