Abstract
Checkpoint blockade immunotherapy (CBT) has revolutionized cancer treatment; however, the cellular and molecular factors that govern responsiveness to immunotherapy remain poorly understood. One emerging area of clinical importance is differential responsiveness to CBT across different tissue sites of tumor growth. Each tissue site in the body can contain unique tissue-resident immune cells from both the lymphoid and the myeloid compartment and differences in tissue-specific immune cell composition might predispose tumors in certain tissue sites to be more or less responsive to immunotherapy. Understanding the interplay between tissue-resident and systemic immune responses against tumors will help to determine how to better therapeutically target the immune system to fight cancer. This review summarizes clinical and preclinical investigations of tissue-specific antitumor immune responses and how they influence the tumor immune microenvironment and the efficacy of immunotherapy.