Department of Surgery Research Day

Department of Surgery Research Day 2017 Abstract Submission Form Deadline: March 17; 6:00 pm EST

Abstract Submission Instructions are provided on the accompanying page. DO NOT CHANGE THE SIZE OF THE ABSTRACT BOX. Minimum font size is 12 point; use Times New Roman or equivalent serif font. Single space the entire abstract. Underline the name of the author who will be presenting abstract. Use an asterisk to identify the senior faculty mentor. Replace “example” in Abstract box with submission. Failure to follow the instructions will result in the abstract not being reviewed.

THE STROMAL INNATE IMMUNE RESPONSE TO PANCREATIC CANCER SUPPRESSES ADAPTIVE IMMUNITY IN A TLR4-DEPENDENT MANNER.

D. Delitto, A. Knowlton, E. Hartlage, B. DiVita, K. Pham, C. Liu, T. George, R. Thomas, K. Behrns, J. Trevino, S. Hughes, S. Wallet*, Departments of Surgery and Oral Biology, University of Florida Colleges of Medicine and Dentistry.

Introduction: Pancreatic cancer (PC) is associated with extensive desmoplasia as well as microenvironmental suppression of antitumor immunity. We hypothesized that the fibrotic tumor-associated stroma (TAS) is activated via an innate immune response to PC cells and, as a direct result, suppresses adaptive immunity. Methods: Primary patient-derived TAS innate immune responses were probed to both known ligands and PC cell conditioned media. TAS innate immune function was then evaluated using both T cell proliferation and cell-mediated lymphotoxicity assays. Results: TAS responded to PC cell conditioned media with robust IL6 and IL8 secretion, representative of the PC microenvironment observed in patients. This TAS secretory response was abrogated by both stromal TLR4 knockdown and pharmacologic IRAK4 inhibition. Conditioned media from the TAS innate immune response suppressed both CD4 and CD8 T cell proliferation in response to anti-CD3/CD28 bead activation, with reduced Th1 and increased Th17 skewing. Further, this TAS innate immune response suppressed cancer cell killing using a transgenic T cell model of patient-derived PC cell lymphotoxicity. Conclusions: Tumor-associated stromal cells respond to secreted factors from pancreatic cancer cells through a TLR4-MyD88 innate immune signaling pathway, subsequently inducing profound adaptive immune suppression. Thus, stromal innate immune modulation represents an important consideration for immunotherapeutic approaches targeting pancreatic cancer.

Abstracts must be submitted electronically using this form by email to [email protected] . The presenting author and the faculty mentor will receive electronic confirmation of abstract receipt. Submission Instructions Department of Surgery Research Day

1. The deadline for electronic abstract submission is March 17 at 6:00 pm EST. Applications should be submitted to [email protected]. Applications will not be considered after the submission deadline. 2. Abstracts may be submitted by house officers, clinical and research post-doctoral fellows, and junior faculty (Instructors and Assistant Professors) whose primary appointment is in the Department of Surgery. 3. For abstract submission, use the example in the space provided. The entire abstract must be singled spaced. The title is in ALL CAPS. The name of the author presenting the abstract should be underlined. The senior faculty mentor should be identified by an asterisk. Use initials and omit degrees. Identify the division from which the research originated, and identify any other departments contributing to the work. 4. Use a structured abstract format, starting with a new paragraph, and identify the Introduction, Methods, Results and Discussion or Conclusions. Do not indent new paragraphs. Figures and tables may be used within the abstract, but must be legible if reduced by 50%. 5. Single space the entire abstract (do not use Exact spacing). Use a 12 point serif font, such as Times New Roman. Do not full justify the margins. Use left justification only. 6. Abstracts will be reviewed by the Department of Surgery Research Advisory Committee for presentation at the Department of Surgery Research Day 2016, April 12 th , 2017. 7. Submission of an abstract to the Department of Surgery Research Day and its presentation as either an oral, quick shot or oral poster presentation fulfills the Department research requirement for categorical house staff. 8. Only abstracts submitted by house staff, medical or graduate students, and clinical or research fellows working within the Department of Surgery will be considered for the “Basic Science” and “Clinical/Translational Science” cash awards. 9. For additional information regarding abstract submission, the review process, and Research Day, contact Dr. Moldawer.