Tumor Host Interactions Program

The goals of the Tumor Host Interactions (THI) Program are to understand both tumor intrinsic and extrinsic conditions of the host that impact tumor initiation, progression and therapeutic response to harness this information using translational pre-clinical studies and clinical trials. THI investigators use expertise in tumor immunology, the 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 tumor microenvironment and site-specific niches.

Scientific Goals

Understand interactions between tumor-intrinsic properties and immune recognition. Existing or treatment-driven tumor heterogeneity can facilitate immune evasion and impaired immune recognition. To understand basic mechanisms and translate these into novel therapeutic approaches, members investigate tumor intrinsic properties such as mutational burden, epigenetics, antigen expression/presentation, and tumor metabolism, as they relate to alterations in the immune microenvironment.

Determine the mechanisms by which host physiologic conditions affect the tumor microenvironment (TME) and tumor progression. The profound hormonal and metabolic changes that accompany puberty, pregnancy, and aging, as well as obesity and autoimmunity, have systemic influences that affect the TME. Host conditions such as age, exposures, metabolic status, and lifestyle choices directly and indirectly impact cancer development and progression by creating a permissive micro-environment, altered therapeutic responses, or predisposition to adverse events. Understanding host physiologic and pathologic conditions that influence cancer enables new prevention and treatment strategies.

Develop innovative therapeutic strategies that redirect the immune system and/or exploit tumor/host interactions. The TME is a complex mixture of tissue components including immune cells, blood vessels, stroma, adipocytes and extracellular matrix that create therapeutic challenges and opportunities. Following pre-clinical modeling, promising strategies are tested in clinical trials. Special emphasis is placed on creating the next generation of immune-focused and cellular therapies. THI members partner with the state-of-the-art Gates Biomanufacturing Facility, with a novel public-private model, to defray costs and prioritize investigator-initiated trials (IITs) that serve the people of Colorado and beyond.

Activities

IrAE meeting series: Immune-related adverse events following cancer immunotherapy is common, but poorly understood.  THI has organized a mini-symposium series to advance collaborations. A diverse group of immunologists, oncologists, endocrinologists and rheumatologists (consulted to treat irAEs) are invited to speak and attend. The inaugural meeting featured researchers funded in irAEs to present and participate in a panel discussion.

Tumor Immunology Forum: The purpose of this bi-weekly meeting is to bring together the basic immunologists, tumor immunologists, and immunology-curious cancer researchers and clinicians. Through sharing ideas and targeted feedback from diverse perspectives, this forum nurtures creativity, fosters collegiality and learning. These interactive meetings typically start with background, rationale, and big picture goals, and data are strategically picked for audience feedback. Presenters are asked to prepare only 30 min of presentation to ensure plenty of opportunity for feedback and discussion. Mentored members are strongly encouraged to present. This meeting averages 45 attendees. 

Multiplex Imaging User Group: This group meets monthly to discuss imaging and analysis related to the technologies and associated experiments offered by HIMSR. HIMSR operates a Vectra instrument that uses immunofluorescence to quantify up to 7 antigens in regions-of-interest, a Vectra Polaris that enables whole-slide quantification, and the Multiplex Ion Beam Imaging (MIBI) that quantifies up to 40 antigens coupled to heavy metal ions in high resolution. Participants actively engage in data presentations, challenges, and peer feedback. Recent topics discussed include high parameter bioinformatic analyses to region selection. 

Breast Cancer U54 Planning: A major priority is to increase multi-PI grants among UCCC members, to enhance cross-disciplinary and collaborative cancer research.

Genetically modified immune-effector cell working group:  With the rising number of investigators turning to genetically modified lymphocytes (T cells, NK cells and monocytes) to target cancer, THI leads a bi-monthly working group discussing preliminary findings, addressing issues of vector design, target identification, transduction methodology, efficacy assays (in vitro and in vivo) and transition to the cGMP facility.  On this latter point, members of the cGMP facility will participate and provide guidance.  While most of this work is performed in THI member laboratories, the working group is open to all campus members.