antiimpotence drugs unmask brst cancer cells to immune system &allow recogntn/attack!

[Lani]

'Erectile dysfunction' drugs heighten natural anti-cancer activity [Eureka News Service]
Sildenafil and other "impotence drugs" that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Johns Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in sildenafil-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system's own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid detection by the immune system by turning elements of that system to its own advantage, says Ivan Borrello, M.D., assistant professor at the Johns Hopkins Kimmel Cancer Center.

Borrello and his colleagues found that tumors exploit nitric oxide-producing immune cells to create a sort of "fog" that keeps them hidden from white blood cells (T-cells) that mount attacks on tumors.

[Lani]

These NO-producing cells, a.k.a. myeloid-derived suppressor cells (MDSCs), normally use nitric oxide to help bring the immune system back down to surveillance levels after an "attack mode" response to foreign material.

The impotence drugs seem to reverse this process, stopping the production of nitric oxide by MDSCs thereby allowing other immune cells to "see" the cancer and attack it, says Paolo Serafini, Ph.D., a research fellow in Borrello's laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of air-polluting smog, but is gaining importance in medical research for its cell-signaling duties and its ability to divert soldiering T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the myeloid-derived suppressor cells and found that sildenafil blocked two genes regulating enzymes — arginase and nitric oxide synthase — which are key to triggering immune suppression via MDSCs. Borrello's team found that the arginase enzyme, which metabolizes a dietary supplement called L-arginine, also contributes to dampening the immune system through MDSCs much like nitric oxide, and its production can be reversed by sildenafil.

"Impotence drugs won't cure cancer," Borello cautioned, "but could be used in addition to standard chemotherapy or immunotherapy treatments."

The investigators are planning human studies to begin in the next year.

[Lani]

ABSTRACT: Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function [Journal of Experimental Medicine]
Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) are agents currently in clinical use for nonmalignant conditions. We report the use of PDE5 inhibitors as modulators of the antitumor immune response. In several mouse tumor models, PDE5 inhibition reverses tumor-induced immunosuppressive mechanisms and enables a measurable antitumor immune response to be generated that substantially delays tumor progression. In particular, sildenafil, down-regulates arginase 1 and nitric oxide synthase-2 expression, thereby reducing the suppressive machinery of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSCs) recruited by growing tumors. By removing these tumor escape mechanisms, sildenafil enhances intratumoral T cell infiltration and activation, reduces tumor outgrowth, and improves the antitumor efficacy of adoptive T cell therapy. Sildenafil also restores in vitro T cell proliferation of peripheral blood mononuclear cells from multiple myeloma and head and neck cancer patients. In light of the recent data that enzymes mediating MDSC-dependent immunosuppression in mice are active also in humans, these findings demonstrate a potentially novel use of PDE5 inhibitors as adjuncts to tumor-specific immune therapy.

[chrisy]

Thanks for posting this - I'm always excited to see research aimed at enlisting our own immune systems to fight cancer, and unmasking those sneaky cancer cells is key.

But taking this to the extreme illogical chain of unintended consequences - if all this viagra succeeds in helping women fight cancer, then they may have more interest in activities of the intimate sort which would seem like a good thing unless their partner suffers from e.d. and coulcn't do anything about it because all the viagra was gone!

An interesting problem - chasing each other around the house fighting over the little blue pills! LOL

Thanks for posting this, Lani - seriously, this is interesting research!

[wiesia]

How much would we have to use to get any benefit ? Any idea ?



wiesia

[Lolly]

Don't know, but I'm willing to be a guinea pig... but really, interesting stuff.

<3 Lolly