BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:EPFL BioE Talks SERIES "Targeting Vasoactive Intestinal Peptide-M ediated Signaling Enhances T Cell Responses to Cancer and Creates Protecti ve Anti-cancer Immunological Memory" DTSTART:20221003T160000 DTEND:20221003T170000 DTSTAMP:20260509T232030Z UID:1d8236225e15267e7e8687a2fd238975e0afea9aa51829a2472d4db7 CATEGORIES:Conferences - Seminars DESCRIPTION:Prof. Edmund K. Waller\, Emory University\, Atlanta\, GA (USA) \nWEEKLY EPFL BIOE TALKS SERIES\n\nAbstract:\nImmune checkpoint molecules are critical targets of cancer therapies due to their ability to modulate immune responses to cancer. Vasoactive intestinal peptide (VIP) has been p roposed as an immune checkpoint molecule\, but its predictive and prognost ic values have not been established. We evaluated expression levels of VIP and programmed death-ligand 1 (PD-L1) across different cancer types and i dentified specific cancer histologies in which the expression of these mar kers is elevated\, including acute myeloid leukemia (AML)\, pancreatic duc tal adenocarcinoma (PDAC)\, and glioblastoma multiforme (GBM). We observed a negative correlation between PD-L1 and VIP expression across cancer typ es\, suggesting the functional redundancy of VIP and PD-L1 immunosuppressi ve pathways as mechanisms of immune escape. We propose that cancer cell ex pression of VIP limits the effectiveness of cellular immunotherapy\, leadi ng to a paucity of effector T cells within the cancer microenvironment\, r endering cancers resistant to immune checkpoint therapies. While several u nder-development approaches target immune-suppressive cells in the tumor m icroenvironment\, there is less focus on improving T cell function.\n\nWe show that inhibiting vasoactive intestinal peptide receptor (VIP-R) signal ing could enhance T cell-dependent anti-tumor immunity in murine models of AML\, PDAC\, and GBM. In silico data mining and immunohistochemistry anal ysis of primary tumors indicate over-expression of the neuropeptide vasoac tive intestinal peptide (VIP) in corresponding human tumor samples. In par ticular\, elevated VIP levels are present in PDAC patient plasma and super natants of cultured PDAC cells. Furthermore\, T cells up-regulate VIP rece ptors after activation\, identifying the VIP signaling pathway as a potent ial target to enhance T cell function. In mouse PDAC and GBM models\, VIP- R antagonist peptides synergize with anti-PD-1 antibody treatment in impro ving T cell recruitment into the tumors\, activating tumor-antigen-specifi c T cells\, and inhibiting T cell exhaustion. In contrast to the limited s ingle-agent activity of anti-PD1 antibodies or VIP-R antagonist peptides\, combining both therapies eliminate tumors in up to 40% of animals. Furthe rmore\, tumor-free mice resist tumor rechallenge\, indicating anti-cancer immunological memory generation. In AML models\, single agent VIP-R antago nists induce complete regression of established C1498 and P815 leukemia in more than 50% of animals\, with cancer-free mice rendered resistant to su bsequent rechallenge with leukemia cells. VIP-R signaling thus represents a tumor-protective immune-modulatory pathway that is targetable in multipl e cancers.\n\nBio:\nEdmund K. Waller\, MD\, PhD\, FACP\, is board certifie d in hematology\, medical oncology and internal medicine. A practicing phy sician with Emory Healthcare since 1995\, Dr. Waller specializes in bone m arrow transplants for acute leukemia\, myelodysplastic syndrome\, myelopro liferative neoplasms\, lymphoma\, aplastic anemia\, sickle cell disease an d in the management of graft-versus-host disease (GVHD). He is also an exp ert in CAR T-cell therapy.\nDr. Waller holds memberships with American Col lege of Physicians\, American Society for Blood and Marrow Transplantation \, American Society of Clinical Oncology\, American Society of Hematology and International Society for Experimental Hematology.\n \nDr. Waller ear ned his undergraduate degree from Harvard University\, his medical degree from Cornell University Medical College\, and his PhD in chemical biology from Rockefeller University in New York\, New York. Dr. Waller completed a residency in the Department of Medicine at Stanford University in Stanfor d\, California. He then went on to complete a clinical fellowship in oncol ogy\, as well as a research fellowship in pathology at Stanford University .\n \n\nDr. Waller's research focus is in enhancing immune reconstitution after stem cell transplant and anti-tumor immunology. He has research sup port from the National Institutes of Health\, The Leukemia & Lymphoma Soci ety and National Marrow Donor Program.\n\n\n\n\nZoom link (with one-time r egistration for the whole series) for attending remotely: https://go.epfl. ch/EPFLBioETalks\n\n\nInstructions for 1st-year Ph.D. students who are und er EDBB’s mandatory seminar attendance rule:\nIF you are not attending i n-person in the room\, please make sure to\n\n\n send D. Reinhard a note b efore noon on seminar day\, informing that you plan to attend the talk onl ine\, and\n be signed in on Zoom with a recognizable user name (not a pseu donym making it difficult or impossible to be identified).\n\nStudents att ending the seminar in-person should collect a confirmation signature after the talk - please print your own signature sheet beforehand (71 kB pdf av ailable for download here).\n\n  LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/ EPFLBioETalks STATUS:CONFIRMED END:VEVENT END:VCALENDAR