New rules of engagement for older patients The body’s immune system does weaken with age, but it also changes, and that changes the rules for fighting disease within the body. Dr. Curiel’s group started by examining an immune therapy that they previously had shown to work in younger hosts, including cancer patients. It’s designed to eliminate regulatory T cells (called Tregs), which are cells that turn off immune responses, allowing cancer to progress. Tregs increase in cancer. In young hosts, the drug turns off Treg activity, allowing the immune system to function better. In older hosts, even though the drug turns off the Tregs, it has no clinical benefit. Dr. Curiel asked the question why, and in this paper his team explains the answer. In older mice, when the drug turned off the Tregs, the researchers found that another type of immune suppressor cell (a myeloid-derived suppressor cell or MDSC) exploded in number to take the Tregs’ place, hampering clinical efficacy. That did not happen in young mice. The team added a second drug that targets the MDSC, and found that with those tools to help immunity, the older hosts can combat cancer just as well as the younger hosts. Adding the second drug afforded no clinical benefit to young hosts, as their MDSC numbers had not increased. “We’ve shown that an aged immune system can combat cancer just as well as a young one if you remove the impediments to successful immunity, which are different than those in younger hosts,” Dr. Curiel said. “We’ve shown that if you test all your immune therapy just in young mice and young people, you’ll never learn how it works in older patients — the ones most at risk for cancer. You might conclude that drugs don’t work in aged hosts, when they do. But they have to be combined with some help.” Human trials on the horizon The next step is to test these concepts in an immune therapy clinical trial for elderly patients, which the research team plans to do, Dr. Curiel said. The drug that is added is anti–Gr-1 antibody and would have to get approval from the FDA, meaning Clinical Trial. With that said, What if we added 5-Fluorouracil to immunotherapy like Yervoy and or Anti-PD1. 5FU immunogenic effects are primarily attributable to MDSC depletion. 5-Fluorouracil selectively kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell–Dependent Antitumor Immunity. This would be the one, two punch for elderly cancer patients. Let's Think outside the box. Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells with the ability to suppress T-cell activation in humans and mice. These cells accumulate in the blood, lymph nodes, bone marrow, and at tumor sites in many human cancers and animal tumor models, and inhibit both adaptive and innate immunit. They notably have the capacity to inhibit CD8+ T cell antigen-specific reactivity by different mechanisms, mainly through their capacities to produce nitric oxide and radical oxygen species.
“It is not the strongest of the species that survives, nor most intelligent, but the one most responsive to change.” ~Charles Darwin~ Take Care, Jimmy B
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