Tumor-Host Interactions Program

University Of Colorado Denver, Aurora CO

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT Overview and Goals: The goals of the Tumor Host Interactions (THI) Program are to understand both tumor intrinsic (Aim 1) and extrinsic (Aim 2) conditions of the host that impact tumor initiation, progression and therapeutic response, and to harness this information using translational pre-clinical studies and clinical trials (Aim 3). THI investigators use expertise in tumor immunology, the tumor microenvironment, and physiology to understand and exploit tumor/host crosstalk, such as tumor-stroma interactions, tumor infiltrating immune cells, heme- and lymph-angiogenesis, endocrine influences on components of the microenvironment and site-specific niches. Research Highlights: Research in Aim 1 demonstrates the role of IL-1 in inflammatory cancers by creating a new IL-1R3 antibody, that blocks 6 different IL-1 family cytokines and shows significant activity in preclinical models (Nat Immunol, 2019 [14]). Exemplifying Aim 2, collaborative research uncovered a novel role of Sema7a in the initiation and progression of postpartum breast cancer (Cancer Res, 2018 [29], Front Immunol, 2019 [30]). This work also identified PDL1 as a potential target for postpartum breast cancer (Oncogene, 2020 [31], Cancer Res, 2020 [32]). In Aim 3, partnerships between the University of Colorado Cancer Center (UCCC) basic researchers, clinical facilities (Children's Hospital and University Hospital) and the good manufacturing production facility create an infrastructure for the production and safe clinical testing of first-in-human cellular therapy. An investigator-initiated clinical trial testing a unique CD19 chimeric antigen receptor (CAR) T product in adults and children is open and a CD19xCD22 product will be tested in Q1, 2021. Program Activities: THI co-leaders employ resources provided by the UCCC to host annual retreats aimed at facilitating intra- and inter- programmatic, multi-investigator collaborations. Programmatic funding is allocated for such efforts, as well as seed grants for junior faculty (many UCCC mentored members). Members: THI has 51 full and 11 mentored members with $4.4M NCI and $7.4M of other peer-reviewed cancer research funding in 2020. Members are from 20 basic science and clinical departments at UCCC affiliated campuses. Since 2016, THI members produced 476 cancer-focused publications, of which 256 (54%) were either inter-programmatic (48%), intra-programmatic (21%), or both (16%); and 162 (54%) represented collaborations with investigators at other NCI cancer centers. Eighteen percent (18%) are in journals with impact factor of 10 or greater. Future Directions: THI will support pilot projects that utilize specialized instrumentation such as CyTOF, MIBI and multispectral imaging that the UCCC invested in to support basic and translational THI studies investigating the tumor microenvironment. Through retreats and strategic workshops, seed grants, and support from relevant SRs, THI will enhance research on the UCCC cross-cutting themes of metabolism and aging in cancer, as well as other tumor intrinsic and extrinsic cell types. THI will collaborate with COE to further understand relevant issues to the catchment, support collaborative science via pilot funding and grow the cellular therapy pipeline for clinical translation.