Myeloid Derived Suppressor Cells in Chronic Myeloid Leukemia Abstract
The suppression of the immune system creates a permissive environment for development and progression of cancer. One population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells (MDSCs), immature myeloid cells able to induce immune-escape, angiogenesis, and tumor progression.
I have long believed CML is a failure of our immune system and that the CML cells themselves contribute the very proteins (cytokines) necessary to "suppress" T-cells from doing their job. I am testing whether my immune system failure is an inherited genetic one (i.e. we are pre-disposed to CML expansion and there is nothing I can do to manage it personally and have to rely on big Pharma) or an environmental one (not enough vitamin D or other nutrients so my immune system was kept in the garage).
This paper summarizes very well why I also believe that one or a million CML cells does not cancer make. Cancer cells are produced all of the time and may even expand and contract over time and we don't even know it. An increasing understanding of our immune systems myriad cell types and protein machinery that must be marshalled in the attack of CML (and other cancers) will no doubt go a long way to relegating cancer to history as a fatal disease. In CML, we have come a long way.
From the paper cited by Gerry:
"Another study reported that patients who had maintained a stable CMR for at least 2 years with Imatinib therapy stopped therapy, but DNA PCR found CML cells again (76). Therefore, in these patients, the immune system is important in maintaining complete remission. In addition, it has been found that NK are important in controlling the leukemic cell growth; in fact, increased levels of NK cell seem to correlate with the successful Imatinib cessation (77). All these observations, together with the finding of BCR/ABL transcripts in some healthy subjects (78), support the idea that in some patients the immunity could exert an immune surveillance against cancer cells, while an inhibition of this control may lead to a permissive environment for development and progression of leukemia."
And this is why I take Curcumin in large enough doses to be "perhaps" effective:
It <curcumin> downregulates the very cells and related proteins CML uses to suppress the immune response as well as downregulate (not inhibit) the Treg cells so they don't interfere with the other T-cells that can destroy CML cells. What a dance that happens in our bodies all of the time between expand or don't expand. On the one hand - rapid proliferation of immune cells is absolutely needed to fight infection (or cancer for that matter). But once the infection is gone (or under control/hibernating like some virus'), these same cells have to decrease in number and become more or less dormant so an autoimmune disease doesn't get started (T-cells attack "self" or good cells). Up and down in population T-cells have to be managed. You might say, Cancer is nothing more than proliferation without a check and reverse switch.
Regarding Curcumin - quoting from the article,
"Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-beta and IL-10 in these cells. More importantly, curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses."
In rebuttal to Trey (from an earlier post) who no doubt will opine on this (hopefully will opine) - having cancer cells in the body occurs naturally. They are produced by the constant bombardment from our environment (chemical carcinogens as well as radiation). Most people have a normal immune system functioning and never know that CML or other cancer cells were produced let alone never expand. Also - for complete edification of my friend Trey - one drop of blood contains over 5,000,000 cells. At the limit of PCR detection - perhaps a million CML cells may remain - which is nothing in terms of the percentage of cells in our blood (1,000,000,000,000 cells of which 2 million red blood cells are made every second). In fact, there is evidence that these remaining CML cells are left over trash (senescence) and are not recognized by the immune system because they are not active. They are not quiescent either. They are done - at the end of being able to divide, but not cleared from the blood. They are the result of a successful destruction of the dividing cells and with a restored immune system don't matter anymore - but they continue to register on the PCR 'meter'. We call this stable MMR.
However - there is the LSC. It remains, quiescent. Keeping it quiescent is one strategy, trying to eradicate it even better, but another strategy is that whenever they divide and produce a leukemic initiating cell, the immune system is primed to attack - just like it does when a herpes virus (cold sore or the other kind) re-activates. I think it is important to stress - the creation of an LSC occurs all of the time due to the wrapping nature of these chromosomes right at the breakpoints where bits of one become bits of another.
Curcumin is no cure - vitamin D is no cure. Taking selenium or other nutrients are not a cure - but neither is a TKI a cure. But taken together, perhaps "control" is a better term than "cure". Our bodies can and do "control" disease. Perhaps we never eradicate anything - or if it is eradicated - it can just be 're-started' as a new disease at some future time. But a new incarnation would have a tough time of it if our immune system is primed and ready.
I look forward to Trey's response.
p.s. - by the way, Trey - here is an excellent article on how DNA breaks produce translocations. You may already be aware of the article:
Disclaimer: CML, like cancer in general, is a serious disease. In Blast phase, CML can be fatal. The continuous taking of a TKI while PCRU is a near guaranteed insurance policy against relapse. Taking a TKI,however, is not without its own risks (both immediate in terms of side effects and long term). I have chosen to take the cessation risk even though I have been breaking the "medical establishment" rules in doing so in order to test the ideas expressed in this thread and my own personal on-going research in other cell biology fields. I do not endorse my approach or recommend it, I merely share it with the forum. I want to live a TKI free life. It's a risk I am willing to take. Others have their own risk profiles. But over time, we will continue to learn more and more about cancer, our immune system and perhaps we will be able to "eradicate" cancer as a "disease" without ever having to eradicate all of the cells in the coming years. This entire immune therapy approach both nutritional and pharmaceutical is exciting indeed.
Edited by scuba, 10 June 2015 - 12:31 PM.
Diagnosed 11 May 2011 (100% FiSH, 155% PCR)
with b2a2 BCR-ABL fusion transcript coding for the 210kDa BCR-ABL protein
Sprycel: 20 mg per day - taken at lights out with Quercetin and/or Magnesium Taurate
6-8 grams Curcumin C3 complex.
2015 PCR: < 0.01% (M.D. Anderson scale)
2016 PCR: < 0.01% (M.D. Anderson scale)
March 2017 PCR: 0.01% (M.D. Anderson scale)
June 2017 PCR: "undetected"
September 2017 PCR: "undetected"