Intraepithelial lymphocytes, Stem cells, Cancer & Sulforaphane

Over the last decade, a new theory of cancer biology has emerged—the cancer stem cell. Normal stem cells are involved in organ repair. Stained here in red, they travel around the body, sit, and wait—until there’s some damage, and step in and replace whatever structures are necessary. Lost a little skin here; bone or muscle there; need to regrow a new tooth? These cells are ready and willing. And, the best part, they’re built to last a lifetime. But those same qualities—migration, colonization, proliferation, self-renewal, immortality—can be used against us, when stem cells go bad, and decide to build tumors instead.

Cancer stem cells may explain cancer spread and cancer recurrence. That may be why cancer tends to come back. There may be no cure; only remission. You can have a breast cancer relapse 20 to 25 years after you thought it went away. Thanks, potentially, to cancer stem cells.

Our current armamentarium of chemo drugs and radiation is based on animal models. If the tumor shrinks, it’s a success. But lab rats only live two or three years. All these new fancy therapies like antiangiogenesis—cutting off the blood supplies to tumors, that’s great, but the cancer stems cells may be like, “Fine, I’ll go somewhere else and grow another tumor.” What we need is to strike at the root of cancer—treatments aimed not at just reducing tumor bulk, but rather at targeting the “beating heart” of the tumor, the cancer stem cell. Enter, broccoli.

Sulforaphane, a dietary component of broccoli and broccoli sprouts, appears to inhibit breast cancer stem cells. Breast tissue naturally has lots of stem cells. Your body never knows when you’re going to get pregnant, and have to start making a lot of new milk glands. Researchers recently discovered this compound in broccoli that may destroy cancerous stem cells, and keep them from going rogue in the first place.

Estrogen-receptor-positive human breast tumor; here’s an estrogen-receptor-negative breast tumor. Let’s add some broccoli juice. Going; going; nearly gone. Stem cell hotspots, before and after the broccoli.

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by veganmontreal.

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The best way to study DNA repair is to study smokers, because they need a lot of it. A group of smokers, for a total of ten days, were asked to eat six times more broccoli than the average American consumes. In other words, a single stalk.

Compared to smokers not eating broccoli, those who did suffered about 30% less DNA damage over those ten days. Maybe it was because the broccoli boosted the detoxifying enzymes in their livers, and so the carcinogens never made it to their DNA?

Well, they tested for that. They actually took some DNA out of their bodies, put it in a test tube, and exposed it to a known DNA-damaging chemical. The DNA of broccoli-eaters suffered significantly less damage. The DNA of those eating broccoli appears intrinsically more resistant at a subcellular level.

“In conclusion, in the present study, the intake of broccoli seems protective, as far as DNA damage is concerned, in smokers who are exposed to oxidative stress.”

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by veganmontreal.

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DOCTOR’S NOTE

This discovery may help explain the findings I presented in Repairing DNA Damage. What about giving smokers kale? See Smoking Versus Kale Juice. And check out my other videos about DNA damage.

Also note that the sources for this video are all open access, so you can click on them in the Sources Cited section, above, and read them full-text for free.

For further context, also see my associated blog posts: Breast Cancer Stem Cells vs. BroccoliKiwi Fruit for Irritable Bowel SyndromeIs Caffeinated Tea Really Dehydrating?Prevent Breast Cancer by Any Greens Necessary; and Foods That May Block Cancer Formation.

If you haven’t yet, you can subscribe to my videos for free by clicking here.

Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.

Our greatest exposure to the environment, our body’s greatest interface with the outside world, is not through our skin, but through the lining of our gut, which covers thousands of square feet. And in our intestine, all that separates us from the outside world is a single layer of cells, 50 millionth of a meter thick. The distance between the outside world and our bloodstream is less than the thickness of a sheet of paper.

In contrast, here’s a layer of skin. Look at that—dozens of layers of protective cells to keep the outside world, outside of our bodies. Why don’t we have multiple layers in our gut wall? Because we need to absorb stuff from food into our body. It’s a good idea for our skin to be waterproof, so we don’t start leaking, but the lining of our gut has to allow for the absorption of fluids and nutrients.

With such a thin fragile layer between our sterile core and outer chaos, we better have quite a defense system in place. And, indeed, that’s where intraepithelial lymphocytes come in. They serve two functions. They “condition and repair” that thin barrier, and provide a “front-line defence against [intestinal] pathogens.” These critical cells are covered with receptors, called Ah receptors. The Ah receptor is like a lock. And, for decades researchers have been searching for a natural key to fit into that lock, to activate those receptors, and sustain our immunity. And, we just discovered the key is broccoli.

Cruciferous vegetables—broccoli, Brussels sprouts, kale, cauliflower, cabbage—contain a phytonutrient that is transformed by our stomach acid into the key that fits into the Ah receptor locks on our intraepithelial lymphocytes, leading to their activation. Here’s a less busy diagram that illustrates the same thing: broccoli leading to the activation of our immune footsoldiers. So, now we know “specific dietary compounds present in cruciferous vegetables act through the Ah [receptors] to promote intestinal immune function.”

“From childhood, we learn that vegetables are good for us, and most of us eat our veggies without giving much thought to the evidence behind this accepted wisdom, or to the mechanisms underlying the purported health-boosting properties of a vegetable-rich diet.” But now, we know that “specific dietary compounds found at high levels in cruciferous vegetables, such as broccoli, cauliflower, and cabbage are essential for sustaining intestinal immune function.” Green vegetables are, in fact, “required to maintain a large population of [those protective] intraepithelial lymphocytes.”

Maybe that’s why vegetable intake is associated with lower risk of inflammatory bowel diseases, such as ulcerative colitis—whereas the more meat-centered Western diet is associated with higher risk of inflammatory bowel diseases. This may be because the activating receptors on our intestinal immune cells are basically “a sensor [for] plant-derived phytochemicals.”

This raises a broader question. Why did our immune system evolve this requirement for broccoli and other plant foods? Well, think about it; when do we need to boost our intestinal defenses the most? When we eat. “Thus, linking heightened intestinal immune activation to food intake could serve to bolster immunity, precisely when it is needed. At the same time, this would allow energy to be conserved in times of food scarcity,” since it takes so much energy. I mean, why remain at red alert 24/7 when you only eat a couple times a day? Since we evolved for millions of years eating mostly weeds—wild plants, dark green leafy vegetables, or, as they were known back then, just, leaves—by equating veggies with food, our bodies may be using them as a signal to upkeep our immune system. Thus, “the old recommendation ‘eat your veggies’ has a strong molecular basis.

This discovery has been all exciting for the drug companies, who are looking into Ah receptor-active pharmaceuticals. “However,” as one research team at Cambridge concluded, “rather than developing additional anti-inflammatory drugs, changing diets which are…currently highly processed and low in vegetable content, may be a more cost effective way towards health and well-being.”

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DOCTOR’S NOTE

Did we really evolve eating that many plant foods? See Paleolithic Lessons.

As remarkable as this story is, this is just the tip of the cruciferous iceberg! See, for example:

 

DOCTOR’S NOTE

Did we really evolve eating that many plant foods? See Paleolithic Lessons.

As remarkable as this story is, this is just the tip of the cruciferous iceberg! See, for example:

 

 

Interest continues to grow about targeting cancer stem cells with a dietary component of broccoli, and especially broccoli sprouts. Cancer stem cells are thought “responsible for initiating and maintaining cancer,” which I’ve talked about in the past.

There’s also been a number of randomized, double-blind, placebo-controlled, clinical trials on the use of broccoli sprouts as a complementary treatment in diabetes, to reduce oxidative stress, reduce inflammation, and reduce insulin resistance and fasting blood sugars. In my video, Biggest Nutrition Bang for Your Buck, I describe how to grow your own—simply and quickly, in five days. New science suggests, though, that it’s even simpler and quicker than I described.

If you look at other sprouts, their antioxidant phytonutrients appear to peak around sprouting day five—up to tenfold higher than day two. But, the sulforaphane content in broccoli sprouts appears to peak at around 48 hours. So, “2-day-old sprouts” may be even better.

“For consumers who do not enjoy eating broccoli [or broccoli sprouts] but still want the benefits” of the broccoli phytonutrients, what about all the “different broccoli supplements…on the market”? Here, they tested BroccoMax, which boasts a half a pound of broccoli’s worth in every capsule. They gave people six a day, compared to a cup of broccoli sprouts. Here’s the spike in broccoli phytonutrients in the bloodstream of those eating sprouts, which would cost about 25 cents a day—compared to six capsules of the supplement, which would cost about two dollars. They conclude that the “bioavailability [of broccoli phytonutrients] is dramatically lower when subjects consume broccoli supplements compared [to the whole food].”

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DOCTOR’S NOTE

Here are links to the videos I mentioned:

What’s so great about broccoli sprouts? See The Best Detox and Sulforaphane: From Broccoli to Breast.

They can be overdone, though; see How Much Broccoli is Too Much?

For more on cruciferous vegetables and cancer, see:

If you haven’t yet, you can subscribe to my videos for free by clicking here.

DOCTOR’S NOTE

Here are links to the videos I mentioned:

What’s so great about broccoli sprouts? See The

 

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract.[1] However, unlike other T cells, IELs do not need priming. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).[2]

Based on expression of either an αβ T-cell receptor (TCR) or a γδ TCR IEL T cells can be divide into two major groups. In mice both groups are retained in almost equal proportions.[3] In humans, the majority of IELs are alpha beta T cells. 15% of IELs are gamma delta T cells and thus represent a minor component of human IELs. However, IELs significantly increase under certain conditions, such as celiac disease.[1]

primary biliary cirrhosis. Bile duct intraepithelial lymphocytes

The majority of IELs (80%) are CD3+, and over 75% of these also express CD8. IELs can be divide into two major subsets based on their CD8 coreceptor expression.[3] One subset of IELs typically express activation marker CD8αα and some IELs express CD8αβ+ marker (CD8αβ promotes TCR activation, whereas CD8αα suppresses TCR signals).

In both humans and mice IELs express higher levels of CD103, activation marker CD69, granzyme B and perforin cytolytic granules. CD25 expression is lower in comparison with effector memory T cells.[4][5]

tInduced IELs (TCRαβ+ CD8αβ+) are generated from naive T cells during an immune response. TCRαβ+ CD8αα (natural IELs) cells differentiate in the thymus.[4][6]

 

EAt sun before

Development and cytolytic activation are independent of live micro-organisms but they become cytolytic in response to the exogenous antigenic substances other than live micro-organisms in the gut. EIL T cells acquired their activated memory phenotype post-thymically, in response to antigens encountered in the periphery.[7]

Their role in immune system is crucial because IELs provide a first line of defense at this extensive barrier with the outside world. All IEL T cells are antigen-experienced T cells, which typically display a cytotoxic functional phenotype. IELs mediate antigen-specific delayed-type hypersensitivity (DTH) responses, exhibit virus-specific CTL function, to express natural killer (NK)-like activity and produce a local graft-versus-host reaction (GVHR) when transferred to semiallogeneic hosts. IELs are also able to produce a variety of cytokines which are characteristically produced by Th1- and Th2-type cells and can also provide help for B cell responses.[4][6][7]

An elevated IEL population, as determined by biopsy, typically indicates ongoing inflammation within the mucosa. In diseases such as celiac sprue, IEL elevation throughout the small intestine is one of many specific markers.[1] IELs have heightened activated status that can lead to inflammatory disease such as IBD, promote cancer development and progression,[8] or become the malignant cells in enteropathy-associated T-cell lymphoma, a lymphoma that is a complication of celiac sprue.[9][10]

Alternatively, elevated IEL populations can be a marker for developing neoplasia in the tissue such as found in cervical and prostate cancers, as well as some colorectal cancers, particularly those associated with Lynch syndrome (hereditary non-polyposis colon cancer <HNPCC>).[11] IELs themselves can, when chronically activated, undergo mutation that can lead to lymphoma.[12]

IEL of the GI tract

  1. ^ Jump up to: a b c Hopper AD, Hurlstone DP, Leeds JS, McAlindon ME, Dube AK, Stephenson TJ, Sanders DS (November 2006). “The occurrence of terminal ileal histological abnormalities in patients with coeliac disease”. Digestive and Liver Disease. 38(11): 815–9. doi:10.1016/j.dld.2006.04.003. PMID 16787773.
  2. ^ Defranco, Anthony L; Locksley, Richard M; Robertson, Miranda. 2007. Immunity: The Immune Response in Infection and Inflammatory Disease. New Science Press Ltd. 218-219.
  3. ^ Jump up to: a b Sheridan BS, Lefrançois L (December 2010). “Intraepithelial lymphocytes: to serve and protect”. Current Gastroenterology Reports. 12 (6): 513–21. doi:10.1007/s11894-010-0148-6. PMC 3224371. PMID 20890736.
  4. ^ Jump up to: a b c Mayassi T, Jabri B (September 2018). “Human intraepithelial lymphocytes”. Mucosal Immunology. 11 (5): 1281–1289. doi:10.1038/s41385-018-0016-5. PMC 6178824. PMID 29674648.
  5. ^ Lambolez F, Mayans S, Cheroutre H (2013). Lymphocytes: Intraepithelial. eLS. American Cancer Society. doi:10.1002/9780470015902.a0001197.pub3. ISBN 9780470015902.
  6. ^ Jump up to: a b Sim GK (1995-01-01). “Intraepithelial lymphocytes and the immune system”. Advances in Immunology. 58: 297–343. doi:10.1016/s0065-2776(08)60622-7. ISBN 9780120224586. PMID 7741030.
  7. ^ Jump up to: a b McGhee, Jerry R. (1998-01-01). “Mucosa-Associated Lymphoid Tissue (MALT)”. In Delves, Peter J. (ed.). Encyclopedia of Immunology (Second ed.). Elsevier. pp. 1774–1780. doi:10.1006/rwei.1999.0448. ISBN 9780122267659.
  8. ^ Cheroutre H, Lefrancois L (2015-01-01). “Chapter 35 – Intraepithelial TCRαβ T Cells in Health and Disease”. In Mestecky J, Strober W, Russell MW, Kelsall BL (eds.). Mucosal Immunology (Fourth ed.). Academic Press. pp. 733–748. doi:10.1016/b978-0-12-415847-4.00035-5. ISBN 9780124158474.
  9. ^ Ondrejka S, Jagadeesh D (December 2016). “Enteropathy-Associated T-Cell Lymphoma”. Current Hematologic Malignancy Reports. 11 (6): 504–513. doi:10.1007/s11899-016-0357-7. PMID 27900603.
  10. ^ Chander U, Leeman-Neill RJ, Bhagat G (August 2018). “Pathogenesis of Enteropathy-Associated T Cell Lymphoma”. Current Hematologic Malignancy Reports. 13 (4): 308–317. doi:10.1007/s11899-018-0459-5. PMID 29943210.
  11. ^ Bellizzi AM, Frankel WL (November 2009). “Colorectal cancer due to deficiency in DNA mismatch repair function: a review”. Advances in Anatomic Pathology. 16 (6): 405–17. doi:10.1097/PAP.0b013e3181bb6bdc. PMID 19851131.
  12. ^ Meresse B, Malamut G, Cerf-Bensussan N (June 2012). “Celiac disease: an immunological jigsaw”. Immunity. 36 (6): 907–19. doi:10.1016/j.immuni.2012.06.006. PMID 22749351.

 

 

 

 

 

 

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