Defining The Inflammatory Signals That Regulate Cd8+ T Cell Recruitment And Function In Colorectal Cancer

Description

My current research has focused on the CD8+ T cell response to infection withinthe tissue and how this is influenced by local inflammation. This application builds onmy prior work, and seeks to examine the role of inflammation in directing productivetissue resident T cell responses to colorectal cancer. My immediate career goal is toacquire an independent faculty position, and subsequently, to lead a research programthat focuses on T cell responses that develop in response to both pathogenicmicroorganisms and solid tumors in the intestinal tissue. The University of Washingtonis an excellent environment for training postdoctoral fellows to become independentresearch scientists. I have been supported by Dr. Bevan and the Department ofImmunology in my research and professional development. The department hasprovided me with the opportunity to present my research and receive feedback, attendresearch seminars in a variety areas including cancer immunology, and encouragescollaboration with affiliated institutions including Fred Hutchinson Cancer ResearchCenter. Many of Dr. Bevan's trainees have gone on to establish successful researchlaboratories, and I believe I have also received the support and guidance necessary tosecure a tenure-track faculty position. It is well established that CD8+ T cell infiltration into solid malignancies, includingcolorectal tumors, positively correlates with tumor control. The majority of intestinalCD8+ T cells are CD103+; however, after infection, a sizable population of CD103– cellsdevelops in the lamina propria in response to inflammatory cues. We hypothesize that aCD103– CD8+ T cell population develops in the intestine during colorectal tumorigenesisand provides superior control of tumor growth, and that inflammation within the tumormicroenvironment promotes the development and function of this T cell population. Thisproposal aims to establish a mouse model of colorectal tumor formation with a definedtumor-associated antigen that will allow us to address questions about the phenotypeand function of tumor-specific CD8+ T cells, the role of CXCR3 in their recruitment intothe tumor, and the role of IL-33 produced by tumor tissue in promoting effector function.I believe my earlier research addressing innate immunity and its influence on adaptiveimmune responses in the tissue provides me with the technical expertise and scientificknowledge to examine the role of inflammation in driving adaptive immune responses incolorectal tumor tissue. The funding provided by this award would provide me with theopportunity to generate reagents and perform the necessary experiments to addressthese questions and develop this new area of research in my laboratory.
StatusActive
Effective start/end date9/1/178/31/20

Funding

  • National Institutes of Health (NIH)

Fingerprint

Colorectal Neoplasms
T-Lymphocytes
Neoplasms
Research
Inflammation
Population
Professional Competence
Adaptive Immunity
Infection
Allergy and Immunology
Innate Immunity
Intestines
Cues
Mucous Membrane
Antigens
Growth