Scientist, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute, Providence Health & Services
Adjunct Clinical Research Assistant Professor, Department of Radiation Medicine, Oregon Health Science University
Research Interests
The Integrative Therapies Laboratory is a collaborative research effort between Dr. Gough and Dr. Crittenden and encompasses their overlapping research interest into the ability of cytotoxic therapy to provide large-scale cancer cell death in vivo, while modifying the profile of immune cells within the tumor. Research projects in the Integrative Therapies Laboratory are investigating the interaction between cytotoxic therapy-induced cancer cell death and the innate and adaptive immune system of the patient.
Current Projects
Cancer patients receive treatment with some combination of surgery, radiation and chemotherapy, and we have reason to believe that the patient’s own immune system may play a role in the success and in the failure of these therapies. As cancers progress, an array of non-cancer cells are co-opted or recruited into the tumor environment. The tumor macrophage is one of the more important cells in this mix since it influences many aspects of the tumor environment. One of our aims is to target the macrophages in the tumor to remove their inhibitory effects and create an environment that supports rather than opposes anti-tumor immune responses. To achieve this aim, we make use of the observation that not all cell death is created equal. As cytotoxic therapies kill cancer cells, other cells, particularly macrophages internalize and destroy the remnants. However, certain modes of catastrophic cell death also release cellular contents that activate inflammatory processes in macrophages that can aid immune responses. Despite such potential adjuvant activity, we have identified that the dysregulated macrophages of the tumor environment respond to inflammatory stimuli with further immune suppression. We are developing strategies to overcome these tumor-supportive and immune-suppressive macrophages through a range of molecular techniques. The goal of this project is to redirect the inflammatory processes that have been subverted to support tumor growth and use the power of the patient’s own immune system to target and destroy the residual cancer cells that remain following treatment.
Research projects in the Integrative Therapies Laboratory encompass basic research, pre-clinical therapy models and translational research through a multi-disciplinary team of Scientists, Physicians and Physician-Scientists to bring novel cancer therapy options to patients.
Recent Publications
Redmond WL, Gough MJ, Charbonneau B, Ratliff TL, Weinberg AD. Defects in the Acquisition of CD8 T Cell Effector Function after Priming with Tumor or Soluble Antigen Can Be Overcome by the Addition of an OX40 Agonist. 2007. J Immunol. 179: 7244-53.2007.
Gough MJ, Ruby CE, Redmond WL, Dhungel B, Brown A, Weinberg AD. OX40 agonist therapy enhances CD8 infiltration and decreases immune suppression in the tumor. Cancer Res. 68(13):5206-15. 2008.
Gough MJ, Weinberg AD. OX40 (CD134) and OX40L [Review – book chapter]. Book: "Therapeutic Targets of the TNF Superfamily". Editor: Iqbal S. Grewal. Publisher: Landes Bioscience. ISBN: 978-0-387-89519-2. Published: 2009
Redmond WL, Gough MJ, Weinberg AD. Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T cell anergy in vivo. Eur J Immunol 39: 1-11. 2009.
Current Research Collaborations
Marka Crittenden, MD, PhD Director of Translational Radiation Research, RWFCRC, EACRI, PPMC, Radiation Oncologist, the Oregon Clinic
Steven K. Seung, MD, PhD Director of Radiation Research, RWFCRC, EACRI, PPMC, Radiation Oncologist, the Oregon Clinic
Todd Crocenzi, MD Director, Gastrointestinal Oncology Research, RWFCRC, EACRI, PPMC Medical Oncologist, the Oregon Clinic
Andrew M. Jackson, PhD Academic Oncology, University of Nottingham, City Hospital, Nottingham, UK.
