researchers discover mechanism of "invsbcloak" brst cancer uses2 hide fr immune systm

[Lani]

UBC Researchers Discover "Instruction Manual" That Tells Cancers How to Hide From Immune System [University of British Columbia]
A mechanism that creates an "invisibility cloak" for certain cancer cells and allows them to hide from the immune system has been uncovered by a team of researchers at the University of British Columbia.
Prof. Wilfred Jefferies and his team found that metastatic tumours (cancers that spread from primary site) can evade the immune system via a process called chromatin remodeling. The invisibility mechanism operates in malignant carcinomas that include ovarian, prostate, melanoma and cervical cancers and is particularly active in breast and lung cancers.
"This discovery begins to address the mysteries of how cancer hides from the immune system and spreads — it helps explain 20 years of observations in the field," says Jefferies, a member of UBC's Michael Smith Laboratories and Biomedical Research Centre. "It may offer whole new avenues for therapies."
Human DNA is packaged within each cell by chromatin, which is made up of DNA that encases proteins called histones. The UBC team discovered that in tumours, chromatin remodelling changes the structure of chromosomes by altering the histone codex or "instruction manual." These changes reduce production of receptors called MHC I molecules that display cancer-specific signals, or tags, recognized by the immune system.
When cancer-specific tags are not displayed, the cancer cells become "invisible" to the immune system and no defenses are mobilized — the tumour cells are free to grow and spread. Furthermore, the high incidence of MHC I loss can be used as a predictor of rapid tumour growth progression and survival rates.
The research has recently been published in Molecular and Cellular Biology. Jefferies is a UBC professor of Medical Genetics, Microbiology and Immunology and of Zoology.
Jefferies says the findings may lead, within five to 10 years, to new therapies that will force the cancer cells to "drop the cloak of invisibility" and be recognized by the immune system. The research team includes A. Francesca Setiadi, Muriel D. David, Robyn P. Seipp, Jennifer A. Hartikainen, and Rayshad Gopaul.
The research has been supported by the National Cancer Institute of Canada; the Prostate Cancer Foundation; the Canadian Institutes of Health Research; the Michael Smith Foundation for Health Research and the Natural Sciences and Engineering Research Council.
ABSTRACT: Epigenetic Control of the Immune Escape Mechanisms in Malignant Carcinomas [Molecular and Cellular Biology]
Downregulation of the transporter associated with antigen processing 1 (TAP-1) has been observed in many tumors and is closely associated with tumor immunoevasion mechanisms, growth, and metastatic ability. The molecular mechanisms underlying the relatively low level of transcription of the tap-1 gene in cancer cells are largely unexplained. In this study, we tested the hypothesis that epigenetic regulation plays a fundamental role in controlling tumor antigen processing and immune escape mechanisms. We found that the lack of TAP-1 transcription in TAP-deficient cells correlated with low levels of recruitment of the histone acetyltransferase, CBP, to the TAP-1 promoter. This results in lower levels of histone H3 acetylation at the TAP-1 promoter, leading to a decrease in accessibility of the RNA polymerase II complex to the TAP-1 promoter. These observations suggest that CBP-mediated histone H3 acetylation normally relaxes the chromatin structure around the TAP-1 promoter region, allowing transcription. In addition, we found a hitherto-unknown mechanism wherein interferon gamma up-regulates TAP-1 expression by increasing histone H3 acetylation at the TAP-1 promoter locus. These findings lie at the heart of understanding immune escape mechanisms in tumors and suggest that the reversal of epigenetic codes may provide novel immunotherapeutic paradigms for intervention in cancer

[dlaxague]

Hi Lani and all,

I read this article elsewhere and because it helps refute a tenacious and often heard (non) "truth" about cancer, I was going to post it here and invite discussion.

The general understanding of most lay (non-cancer) people that I talk to is that a weak immune system is at fault, when cancer is "allowed" to develop and/or grow. Or conversely, that we can resist or fight cancer by strengthening our immune functions.

From this premise comes the even more often heard "truth" - that stress causes cancer by weakening the immune system ( that last part is true - some stress can affect some immune functions). But what is not true is that the stress causing the weakening has an effect on the stealthy cancer.

They've know for some time that cancer is often not recognized as a threat by the immune system, thus (again), it's not that a weak response is mounted by a weak immune system - it's that NO response is mounted by an oblivious (or hoodwinked) one. That's why vaccines offer promise - they might be able to help the immune system recognize a cancer and mount an offense against it.

Another aspect of this is another often-heard story - that everyone has cancer cells develop in their body (even daily perhaps) and that they are taken care of by the immune system. Probably true. But those cells that are mopped up daily are those with the poor clandestine skills - they are unable to evade detection. The clever, stealthy ones are the successful cancers. And they are successful because of some excellent (depending of course upon perspective) skills of the cancer cell, not because of some lack in the immune system.

Debbie Laxague

[StephN]

"Jefferies says the findings may lead, within five to 10 years, to new therapies that will force the cancer cells to "drop the cloak of invisibility" and be recognized by the immune system"

Quote from the above article. Let's all fervently hope and pray that someone will crack this problem long before 5 or 10 years! PLEASE.

This article backs up just what my med onc told me over 7 years ago when my cancer was found. He told me that "there was NOTHING wrong with my immune system" and that this cancer flies low under the radar of even the healthiest immune systems. He said that much was known and that he knew several groups were working to understand the inner workings of that stealth system those rogue cells have.

Thanks Lani - I have been waiting for this news a long time!