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VERSION:2.0
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SUMMARY:EPFL BioE Talks SERIES  "A Novel Role of IL-10 in Preventing T-Cel
 l Exhaustion and Maintaining Anti-tumor Immunity"
DTSTART:20221031T160000
DTEND:20221031T170000
DTSTAMP:20260916T080902Z
UID:7bbdb86cf260db5ed05ddad85055936fd8e5bcb46b9f8cec860977be
CATEGORIES:Conferences - Seminars
DESCRIPTION:Martina Seiffert\, Ph.D.\, Group leader – Immune Modulation 
 in Cancer\, German Cancer Research Center (DKFZ)\, Heidelberg (DE)\nWEEKL
 Y EPFL BIOE TALKS SERIES\n\nAbstract:\nChronic antigenic stimulation in tu
 mors drives T-cells into terminal differentiation or “exhaustion”\, a 
 cell state that is characterized by the expression of inhibitory receptors
  like PD-1\, and the loss of proliferative and functional properties. We e
 xplored microenvironmental signals regulating this process. Using single-c
 ell analyses\, we identified a subset of CD8+ effector T-cells with high (
 hi) PD-1 expression and exhausted phenotype that accumulated in secondary 
 lymphoid organs of mouse models and patients with chronic lymphocytic leuk
 emia (CLL) during disease progression. These T-cells were transcriptionall
 y distinct from less differentiated cells with intermediate (int) PD-1 exp
 ression which showed a higher functional competence. The balance between t
 hese two CD8+ T-cell subtypes was regulated by interleukin-10 (IL-10) rece
 ptor signaling. Genetic depletion or blocking of IL-10 receptor signaling 
 resulted in a dramatic loss of the PD-1(int) subset and an accumulation of
  activated but dysfunctional PD-1(hi) cells\, leading to a significantly e
 nhanced tumor development. Mechanistically\, IL-10 receptor blockade alter
 ed chromatin accessibility and disrupted the cooperativity of the transcri
 ption factors NFAT and AP-1 in CD8+ T-cells. Analyses of clinical data rev
 ealed that low IL-10 expression or loss of IL-10 receptor signaling correl
 ated with poor survival and enhanced CD8+ T-cell exhaustion in cancer pati
 ents. Thus\, IL-10 receptor signaling prevents activation-induced exhausti
 on of tumor-reactive CD8+ T-cells\, which could be exploited for improving
  immunotherapy.\n\nBio:\nMartina Seiffert is heading the group «Immune Mo
 dulation in Cancer» within the Division of Molecular Genetics at the Germ
 an Cancer Research Center (DKFZ) in Heidelberg\, Germany. She is intereste
 d in immune modulatory mechanisms in the tumor microenvironment\, with a f
 ocus on B-cell lymphoma and brain metastases.\nUsing innovative single-cel
 l omics approaches\, her team analyses the immune and stromal compartment 
 of tumors to decipher tumor-supportive and immunosuppressive mechanisms an
 d to suggest novel immunotherapy targets. The lab has established various 
 coculture models of primary patient samples\, as well as mouse models\, th
 at are used for studying disease biology as well as for pre-clinical testi
 ng of drugs. They recently identified the L-amino acid oxidase IL4I1 as a 
 novel metabolic immune checkpoint that contributes to immune escape in can
 cer. The group has further demonstrated a novel role of IL-10 in preventin
 g T-cell exhaustion and maintaining anti-tumor immunity.\nAfter studying b
 iology at the University of Constance\, Germany and the University of Oreg
 on\, Eugene\, USA\, Dr. Seiffert obtained her PhD at the University of Tü
 bingen\, Germany\, investigating the bone marrow microenvironment in hemat
 opoietic malignancies. As a postdoctoral fellow\, she continued her resear
 ch at the University of Tübingen and the Fred Hutchinson Cancer Research 
 Center in Seattle\, USA\, focusing on oncogenic signaling in malignant and
  stromal cells in cancer. \n\n\nZoom link (with one-time registration for
  the whole series) for attending remotely: https://go.epfl.ch/EPFLBioETalk
 s\n\n\nInstructions for 1st-year Ph.D. students who are under EDBB’s man
 datory seminar attendance rule:\nIF you are not attending in-person in the
  room\, please make sure to\n\n	send D. Reinhard a note before noon on sem
 inar day\, informing that you plan to attend the talk online\, and\n	be si
 gned in on Zoom with a recognizable user name (not a pseudonym making it d
 ifficult or impossible to be identified).\n\nStudents attending the semina
 r in-person should collect a confirmation signature after the talk - pleas
 e print your own signature sheet beforehand (71 kB pdf available for downl
 oad here).\n\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/
 EPFLBioETalks
STATUS:CONFIRMED
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