AbstractThe molecular interactions underlying regulation of the immune response take place in a nanoscale gap between T cells and antigen-presenting cells, termed the immunological synapse. If these interactions are regulated appropriately, the host is defended against a wide range of pathogens and deranged host cells. If these interactions are disregulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Strategies targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. This Masters' primer will cover the basics of the immunological synapse and some of the applications to tumor immunology. Cancer Immunol Res; 2(11); 1023–33. ©2014 AACR.