Possible Link Between Gut Bacteria and PD-1 Inhibitor’s Ability to Combat Advanced Melanoma

PD-1 Inhibitors & Gut Bacteria

Researchers from the University of Chicago are now finding a commonality connecting the presence of certain intestinal bacteria and the efficiency of PD-1 Inhibitors given to Melanoma patients.

   What is PD-1?:

Programmed Cell Death Protein 1, frequently referred to as PD-1, is an immune checkpoint on the surface of a T-Cell. Its main function is to determine if another cell present in a person’s body should be attacked or left alone. The selection method is based on whether or not the PD-1 of a T-Cell can bind with a PD-L1 of an opposing cell. If a bond is made, it acts as a switch and the cell in question will be left alone by the immune system. Cancer cells can often contain large amounts of PD-L1, which helps it evade the body’s innate defenses.

With this in mind, medicine-makers began manufacturing PD-1 Inhibitors. These drugs are designed to interrupt the protein binding process that allows the cancer cells to develop unperturbed. With the pathway between PD-1 & PD-L1 blocked, a healthy immune system can respond to the tumor.

Common Manufactured Protein Inhibitors:

• Nivolumab [Opdivo]
• Pembrolizumab [Keytruda]
• Ipilimumab [Yervoy]
• Avelumab [Bavencio]
• Atezolizumab [Tecentriq]

These protein inhibitors, along with the practice of immune signal interference as a whole, show great promise in the advancement of cancer therapy; however just over a third of all melanoma patients who received these treatments showed a considerable improvement in their condition.

Looking for answers, researchers began observing & experimenting with the gut bacteria of patients involved in the study. The University of Chicago Medicine Team had already known from previous works that intestinal microbes played a part in the usefulness of immunotherapy on mice, so they began examining its significance with humans.

The scientists separated the bacteria samples into two groups, one from patients who responded well to the PD-1 Inhibitors and the other of those who had not. They began seeing similarities in the kinds of bacteria showing up in both cross sections. A clear picture started to form of which microorganisms were favorable to a positive PD-1 Inhibitor reaction. Contrarily, there were certain different bacteria types present in the non-responses as well.

Immediately tests began with the intention of seeing how rapidly tumors would grow in mice that were earlier injected with the various bacteria found in the patient groups.

The results made clear that the kinds of intestinal bacteria present in an individual have major connection with how well an immune system can respond to a tumor, especially when a PD-1 Inhibitor-type drug is administered. These naturally occurring microorganisms were only thought to have a slight role in this process, but through these studies it was found to be a major predictor in whether the treatment would work actually work.

Revelations like this will only lead to more research on immunotherapy, especially concerning the microbial relationships that increase or diminish a treatments success.

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