Cancer immunotherapies, such as checkpoint blockade and adoptive cell transfer, have achieved unprecedented clinical responses in some patients, however there is still a long way to go to extend the success from a small fraction to all cancer patients. Immune evasion and immune suppression are central issues in innate and acquired resistance to cancer immunotherapies. It is known that tissue stem cells have certain “immune privileges” which are important to avoiding immune destruction and maintaining tissue homeostasis. It is also known that the mechanisms of stem cell immune privilege can be hijacked by tumor cells to evade immune destruction. However, whether and how the mechanisms of stem cell immune privilege are connected to the immune suppressive tumor microenvironment and resistance to immunotherapy is not clear. Thus, the goal of this National Cancer Institute organized workshop is to assess the mechanisms of stem cell immune privilege, including tissue stem cells and cancer stem cells, and how these mechanisms might be related to the immune evasion and immune suppressive microenvironments in tumors. Gaps in our current knowledge and challenges/opportunities for improving cancer immunotherapy will be discussed.