Although tumor antigens are expressed by the majority of cancers, and T cells can be generated than can kill antigen-expressing tumor cells in vitro, T cell-based immunotherapies in the clinic have yielded only modest success. Active immunization and adoptive transfer of specific T cell populations can increase the frequency of functional tumor antigen-specific T cells in the blood. However, only a subset of patients experiences a clinical response in the absence of additional manipulations. The fact that the presence of circulating anti-tumor T cells does not always lead to tumor regression has pointed to intense study of the tumor microenvironment for key features that may dictate whether or not tumor regression occurs. This session will focus upon several key characteristics of the solid tumor microenvironment, using both mouse model systems and analysis of human samples, that regulate the effector phase of the anti-tumor immune response. Critical regulatory checkpoints include whether or not the tumor: 1) expresses chemokines for T cell migration, 2) shows activation of the vasculature to allow inflammatory cell trafficking, 3) contains immune suppressive factors that inhibit T cell function, 4) induces innate immune factors such as type I interferons, and 5) depends heavily on stromal cells that support tumor growth and whether these are simultaneously immunologically destroyed with tumor cells. Identification of these key factors that influence the effector phase of anti-tumor immune responses has pointed towards new therapeutic approaches to be evaluated in patients.
Symposium: Immune Regulation in the Tumor Microenvironment

Regulation of T-cell homing to tumors; George Coukos. Univ. of Pennsylvania Medical Ctr., Philadelphia, PA

Immune destruction of the tumor microenvironment; Hans Schreiber. Univ. of Chicago, Chicago, IL

Th17 cells in the tumor microenvironment; Weiping Zou. Univ. of Michigan School of Medicine, Ann Arbor, MI

Immune regulation from within the solid tumor microenvironment; Thomas F. Gajewski. Univ. of Chicago, Chicago, IL,