Cancer Can't Breathe (or Grow) with No AIRE || Sophia Guldberg

Life is all about balance. We all try to balance work, family, hobbies and more daily. But today, I want to talk to you about a balance you probably never think about and your immune system between rejection and tolerance. This balance is an incredibly complex process of give and take between the various players of our immune system and also the key to keeping us healthy. Tip too far towards rejection and you get autoimmunity or allergies, but tip too far towards tolerance and you develop cancer

s specifically. In the case of cancers, the balance has become skewed. So the immune system no longer recognizes mutated cells as disease and fails to eliminate them. The obvious solution to this is to restore the balance and help the immune system recognize the cancer is disease once again. But if it's this simple, why haven't we cured cancer? We haven't cured cancer because cancer is very good at disguising itself. And while great advancements have been made on therapies that enhance our immun

e systems, far too many patients still die of cancer. I, with the help of my collaborators, have spent the last several years studying how this healthy balance tips towards tolerance in cancers through the study of a gene called AIRE, also known as autoimmune regulator gene. AIRE is known to teach the immune system to tolerate and recognize healthy cells. This is incredibly important to establishing immune balance, but I ask the question of whether immune cells expressing Aire might inadvertentl

y teach the immune system to tolerate cancer, which, as I previously mentioned, is very good at disguising itself. At first it wasn't even known that immune cells in a tumor could express Aire. However, I recently discovered not only can they express Aire, but that when I eliminate these Aire expressing immune cells, I can promote tumor rejection in mouse models of cancer. For our team, this is an incredibly exciting result because it means that we found a way to boost the immune system and help

it recognize the cancer is disease once again. In order to look at these cells more specifically, I wanted to understand why elimination of air expressing immune cells is effective at slowing tumor growth and then found that elimination of these cells allows the remaining immune cells to become less tolerant and more prone to rejection, enabling them to recognize the cancer as disease and kill it. Now, knowing that Aire expressing immune cells are helping to tip the balance towards tolerance to

cancer, I want to further understand how immune cells take on this more tolerant role and to understand whether we can target these Aire expressing immune cells, specifically using therapies already approved by the FDA in other indications. I hope that our studies will be a breath of fresh air into the field of cancer therapeutics and allow us to continue to care more patients of cancer every day. And that is the power of balance. Thank you.