Cancer researchers have found that the immune system plays an important role in cancer. Our immune system I programmed to kill cancer cells. But, cancer cells eventually develop ways to escape the immune system and grow and spread. While it is unclear how this happens, many scientists are now developing therapies to reactivate the immune system to attack cancer cells. This field is called immunotherapy. While promising, we are still in early days, and there is much about the cancer immunology we don’t understand. Through our studies, we have identified a protein called APOBEC3A that might prevent the immune system from destroying cancer cells. APOBEC3A is an interesting protein since it is found in high amounts in many types of cancers, including lung, breast, colon and pancreatic cancer. Here, we will try to understand how APOBEC3A exactly affects the immune system in cancer. Secondly, we have found that human and mouse tumors that have high levels of APOBEC3A also tend to have high levels of molecules that specifically stop immune cells from attacking cancer cells called checkpoints. In a novel preclinical trial, we will see if a combination of drugs that target these molecules can effectively treat cancers that express high levels of APOBEC3A. If this trial works in mice, then this approach may be lead to a new treatment strategy in a subgroup of patients with many types of cancer, including pancreatic cancer.