Chief, Laboratory of Immunological Monitoring, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute, Providence Health & Services
Research Interests
The Laboratory of Immunological Monitoring focuses on measuring patients' immune responses to different immunotherapy interventions, such as experimental cancer vaccines, to assess vaccine effectiveness. Highly sophisticated polychromatic flow cytometry techniques allow scientists to measure immune responses on a cellular level. The results help researchers refine their studies and improve vaccines. Dr. Walker and his team are leading national efforts to develop optimal procedures for monitoring cancer patients' responses to immunotherapy.
Current Projects
Data from human cancer vaccine trials suggest that repetitive vaccination with MHC class I tumor-associated peptides in the absence of class II helper T cell (Th) epitopes may result in attenented long-term CD8+ memory T cell differentiation and function. Such attenuated tumor-reactive memory T cells may express phenotype and functional properties similar to those of memory T cells stimulated by chronic viral infections such as CMV. The attenuated anti-tumor memory T cell responses observed in previous tumor-peptide vaccine trials may have been due in part to the more compromised immune status of patients with advanced disease.
Using cryopreserved post-vaccine therapy lymphocytes from early stage I-III melanoma patients the Laboratory of Immunological Monitoring will compare in detail the subphenotype signature and functional properties of tumor antigen-specific CD8+ memory T cells from patients with progressive disease to those who are disease-free. Parallel correlated analysis of CMV and Flu-specific memory T cells in each melanoma patient will further characterize any significant functional or phenotype differences between tumor antigen-specific memory and effector T cells and those specific for chronic (CMV) and acute (Flu) viral antigens. Importantly, this analysis employs the comprehensive discriminating power of newly evolved polychromatic (9- to 12-color) flow cytometry technology to characterize tumor antigen-specific CD8+ memory T cells in greater detail than has been previously reported.
Ongoing studies in Dr. Walker's laboratory will continue to focus on the in vitro effects of IL-15 and IL-21 on the proliferation and maintenance of tumor antigen-specific central memory (Tcm) and effector memory (Tem) CD8+ T cells in both murine and human cells. In vivo translational studies in murine tumor models will emphasize the analysis and optimization of combined tumor antigen specific immunization and either IL-21 or IL-15 cytokine therapy in tumor-bearing lymphopenic mice.
Development of effective immunotherapy for prostate cancer patients (DOD PC020094 – PI: Bernard Fox)
Clinical:
Brendan Curti, MD – Director of Genitourinary Oncology Research, Providence Portland Medical Center
Exploiting lymphopenia and depletion of CD25+ regulatory T cells to augment effective immunotherapy (Prostate Cancer Foundation – PI: Bernard Fox). www.prostatecancerfoundation.org
Clinical:
Walter Urba, MD, PhD – Director of Cancer Research, Providence Portland Medical Center
Brendan Curti, MD – Director of Genitourinary Oncology Research, Providence Portland Medical Center
