Unlocking the Potential of Immunotherapy: Targeting AMPK for Improved Anti-Tumor Activity

The cells of the immune system, and especially dendritic cells (DCs) and T cells, play a vital role in the defense against cancer. Therefore, there is great interest in developing immunotherapies that improve the anti-tumor activity of these cells. Like all cells, DC and T cells need nutrients to function properly. But tumors are often so depleted of nutrients that DC and T cells no longer work properly.

Research directions/suggested solution

We have discovered that as a result of this restriction of nutrients in tumors, the AMPK protein becomes active in DCs and T cells, which we found in experiments to inhibit the activity of these cells . Thus antagonizing AMPK activity in these cells in a tumor provides an exciting new opportunity to enhance their anti-tumor activity.

Belonging

Current immunotherapies against cancer still do not work well in many cases because DC and T cells are often blocked in their work in tumors. So it is important to find out if AMPK activity plays a role in this, so that we can combat it and make immunotherapies more effective.

Research questions

In the current project we want to investigate the mechanism by which AMPK activation limits the activity of DC and T cells and determine whether AMPK inhibition in these cells has potential in tumorigenesis improve existing immunotherapies.

Research design

First we want to investigate what happens to the anti-tumor immune response when we remove AMPK from DC and T cells, using mice in which AMPK has been genetically deleted specifically in the DCs or T cells. We then want to know in which way AMPK activation leads to inhibition of DC and T cell function. We will investigate this in experiments with cultured DCs and T cells In the third part of this project, we want to find out in an animal model whether inhibition of AMPK signaling in a therapeutic setting can improve anti-tumor immune responses in combination with other forms of immunotherapy. In addition, we will test whether inhibition of AMPK can improve the activation of DC and T cells derived from tumor tissue of skin and colon cancer patients.

Expected outcomes

The experiments described will identify how AMPK activity directly affects DC and T cell activity in tumors. Furthermore, we expect that inhibition of AMPK activity in DC and T cells will lead to a significant anti-tumor immune response, leading to a better clinical course.

Steps required to implement results

In follow-up studies, it will first be necessary to test on a larger scale whether inhibition of AMPK activity can improve the activity of DCs or T cells from different types of cancer patients and how long AMPK inhibition has an effect before it can for him to be. tested in clinical studies. For clinical translation, the availability of clinically approved AMPK inhibitors is also essential, which is currently not the case. Our research allows us to make this clinical translation.