Saturday, January 11, 2014

Vitiligo and melanoma

Vitiligo, caused by the destruction of melanocytes, cells that give our skin pigment, leaving patients' with white blotches on their skin in their absence, has long been realized to be a positive/hopeful sign when it occurs in patients with melanoma.  On extremely rare occasions it begins spontaneously, at other times it follows treatment with immunologic agents like IL2, ipi and anti-PD1.  However and whenever it occurs, the data shows that those patients have a better prognosis than many of their counterparts, with a rough doubling of 10 year survival in Stage IV patients. (Latest pics of my vitiligo are posted on the March 29, 2013 guess we'll find out what happens to me as we go along!!!)  Additionally, vitiligo can occur in folks with no melanoma or treatments (think MJ here) and in fact, 0.4% of Caucasians in the United States have it.  However, we don't really understand it in either case.  What does seem important, is that if vitiligo indicates that the body is getting rid of melanoma cells, then we do need to know better how to induce it in melanoma patients!

Autoimmune Vitiligo Does Not Require the Ongoing Priming of Naive CD8 T Cells for Disease Progression or Associated Protection against Melanoma.  
Byrne, Zhang, Steinberg, Turk.  Journal Of Immunology, 2014, Jan 8, [Epub, ahead of print]

Vitiligo is a CD8 T cell mediated autoimmune disease that has been shown to promote the longevity of memory T cell responses to melanoma.  However, mechanisms whereby melanocyte/melanoma Ag-specific T cell responses are perpetuated in the context of vitiligo are not well understood. These studies investigate the possible phenomenon of naive T cell priming in hosts with melanoma-initiated, self-perpetuating, autoimmune vitiligo.  Using [a certain kind] of CD8 T cells, we demonstrate that autoimmune melanocyte destruction induces naive T cell proliferation in skin-draining lymph nodes...  These...T cells upregulate expression of CD44, P-selection ligand, and granzyme B.  However, they do not downregulate CD26L, nor do they acquire the ability to produce IFN-y, indicating a lack of functional priming. Accordingly, adult thymectomized [removal of the thymus gland because it has a role in central memory T-cells....poor little ratties!!!] mice exhibit no reduction in the severity or kinetics of depigmentation or long-lived protection against melanoma, indicating that the continual priming of naive T cells is not required for vitiligo or its associated antitumor immunity.  Despite this, depletion of CD4 T cells during the course of vitiligo rescues the priming of....T cells that are capable of producing IFN-y and persisting as memory, suggesting an ongoing and dominant mechanism of suppression by requlatory T cells. This work reveals the complex regulation of self-reactive CD8 T cells in vitiligo and demonstrates the overall poorly immunogenic nature of this autoimmune disease setting.

WHEW!!!!  Feel like I just typed in that pretend language my sisters and I would "talk" in with each other as kids!

What I think this says is:  The CD8 T cells that cause vitiligo, promote response to melanoma.  But, we don't know how. So...the researchers checked a certain type of T cell in mice with no thymus (so the mice couldn't use that part of the process to induce vitiligo) and even so, the active T cells continued to produce vitiligo and protection against melanoma.....and they don't know why!

Anyhow, Mary Jo Turk, one of the authors, is the researcher Brent contacted some time back. We tried to connect her research with Weber (he gave his blessing for her to call) so that perhaps my lab results and cells collected could be analyzed in hopes of finding more answers to the vitiligo conundrum...but it doesn't seem that anything ever came of it.  Perhaps it will someday.  B has emailed her some questions regarding this article and if I've got it all wrong or I learn new nuggets, I'll pass them along.

Meanwhile, ran a couple miles in outright balmy weather with birds chirping as though spring were near.  A huge change from the -2 degrees we had here on the mountain just a few days ago!!!  Stay warm! - c

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