The central theme of the Tumor Microenvironment Program of the USC Norris Comprehensive Cancer Center (NCCC) is the investigation of basic mechanisms of interaction between malignant cells and their microenvironment. The overarching goals of the Program are to promote the translation of fundamental observations into the identification of novel targets for therapeutic intervention and the identification of better prognosticators that can both be tested in preclinical models by Program members and in human clinical trials in collaboration with other programs in the NCCC. The Program consists of 24 members from 11 departments and two schools, located at both Childrens Hospital Los Angeles (CHLA) and Keck School of Medicine (KSOM) campuses, with a complementary expertise in cell biology and immunology. It has three primary areas of focus: 1) angiogenesis, vasculogenesis and lymphangiogenesis; 2) cancer-stroma interaction; and 3) immunology and immunotherapy. Members of the Program are funded by a total of $7.4 million of direct costs in extramural peer review funding, including $2.7 million from the NCI and $4.5 million from other NIH institutes. Over the last five years, members of the Program have published a total of 408 scientific publications, including 64 intra-programmatic and 151 inter-programmatic publications. The Program has substantially grown over the last five years with a 30% increase in extramural peer review funding and 59% increase in NCI funding since 2005. The Program has become increasingly interactive, as indicated by an increase in the percent of intra- and inter-programmatic publications from 28% in 2000-2004 to 53% in 2005-2009. Over the last funded period, with the strong support of the NCCC, the Program has also made significant progress in recruiting eight new faculty members, in promoting interactive and transdisciplinary research, in translating some fundamental discoveries made in the laboratory to the bedside (in particular in neuroblastoma bone metastasis, Kaposi sarcoma, melanoma and human papilloma virus (HPV)-related cancers), and in broadening the scope of its expertise in immunology, cytokines and signaling. It is anticipated that the Program will continue to play a pivotal role in identifying novel microenvironmental targets for therapeutic intervention that will be tested in combination with more conventional treatments in patients with a variety of cancers, in particular children and women.