Classic Hodgkin lymphoma (cHL) is a common cancer in children and young people. While current treatments cure many patients, they often involve intensive chemotherapy and radiation that can cause serious long-term side effects. New, safer treatments are needed. Immunotherapy drugs that target a protein called PD-1 help the immune system attack cancer and are already used in cHL. However, many patients do not have lasting responses, meaning the cancer can return. This project aims to understand why some patients develop resistance to these treatments and how to overcome it. Our research focuses on the tumor “microenvironment,” the mix of cells surrounding cancer cells. We have found that certain immune cells can actually suppress the body’s ability to fight the cancer, contributing to treatment resistance. We will study patient samples to identify markers that predict who will respond to PD-1 therapy and who will not. We will also test a drug called entinostat, which may improve immunotherapy by changing the tumor environment and reducing these suppressive immune cells. Using laboratory models and patient data, we aim to design better combination treatments. Ultimately, this work could lead to more effective and less toxic therapies for young people with cHL.