One of cancer’s greatest tools is its ability to manipulate the immune system. Many cancer therapies have arisen targeting this defense mechanism, such as the many PD-1 drugs developed over the last several years.
The immune system is the body’s primary defense to both everyday issues and foreign invaders. It surveys the body looking for problems, and when it finds them, it induces an immune response to clear out the problem cells or invaders. Cancer cells produce many abnormal signals that would cause the immune system to find and destroy the cell, but sometimes it develops a sort of defense. Cancer cells will passively produce signals that inactivate the immune response, effectively halting the body’s natural anti-cancer machinery.
It stands to reason that targeting cancer’s ability to inactivate the immune system would make for a good therapy then. Well, over a decade ago, scientists thought the same. The go-to target became the proteins PD-1 and PD-L1, both critical regulatory elements of the immune system. PD-1 is a protein on the surface of immune cells that inactivates the immune system’s “attack” response. The protein PD-L1 normally inactivates this to keep the immune system from attacking healthy cells. Cancer cells use this to their advantage, with some types of cancer overexpressing PD-L1 and keeping the immune system inactive anytime it gets close.
In a new study out of the University of Michigan Medical School, a team of scientists wanted to investigate another aspect of the immune system, platelets. Platelets are a sort of pseudo-cell that play a role in some immune responses like inflammation. Some research has suggested they are also able to protect tumor cells from the immune system. In this study, the team examined how PD-L1 from platelets affects cancer cells.
The team found that platelets could indeed protect cancer cells from immune cells in vitro. Platelets alone were also able to suppress the immune response in vitro. They used a PD-L1 negative cancer cell line (a line that did not have the PD-1 defense) and saw that with the addition of activated platelets, there was an increase in PD-L1 on the cancer cells’ surface. Inhibiting the activation of platelets even led to enhanced effectiveness of PD-1 based chemotherapies, suggesting that platelets may play a role in cancer resistance.
This study found that platelets can protect cancer cells by suppressing the immune response against them. In vitro evidence found that in PD-L1 negative cancer cells, activated platelets could coat cancer cells in PD-L1. They also saw that the addition of platelet inhibitors could enhance the immune system’s response against cancer cells.
The study concludes, “Our experiments validate and expand on previous observations that platelets modulate the immune system to support cancer growth and implicate platelet PD-L1 as operational in this process.”
Sources: Nature Scientific Reports, Genentech, Unsplash