okt
2020
Online
Welcome to the Sahlgrenska Academy Science Seminars – SAS-seminars, a series of seminars on Thursdays at 15-16. The seminars are, during fall 2020, conducted through Zoom Webinars.
The seminars are open to anyone interested in taking part of scientific breakthroughs and projects in the medicine and health science field, scientists, students and other staff from GU, VGR and other organisations with the common interest of medicine and health science.
Topic:
Chronic antigenic stimulation of T-cells in cancer induces their terminal differentiation or “exhaustion” which contributes to immune escape of tumors. We explore microenvironmental signals regulating this process and describe an unexpected mechanism of IL-10 preventing activation-induced exhaustion of tumor-reactive T-cells in chronic lymphocytic leukemia (CLL). Within CD8+ effector T-cells that control CLL progression, we identified a population of exhausted PD-1hi cells that accumulate in secondary lymphoid organs of CLL patients, and are transcriptionally distinct from PD-1int cells that maintain functional properties. We show that the balance between these two CD8+ T-cell subsets is regulated by IL-10R/STAT3 signaling. Using ATAC-seq, we observed that IL-10 receptor blockade alters chromatin accessibility and disrupts the cooperativity of the transcription factors NFAT and AP-1 in CD8+ T-cells leading to a dramatic loss of the PD-1int subset and an accumulation of dysfunctional PD-1hi cells. Accordingly, T-cell mediated control of CLL in mice is compromised following IL-10 receptor blockade. We further show that loss of IL-10R/STAT3 signaling correlates with CD8+ T-cell terminal differentiation and poor survival in cancer patients. Taken together, our data demonstrate the central role of IL-10/STAT3 signaling in modulating chromatin states of CD8+ T-cells preventing their exhaustion, and suggest this mechanism as therapeutic target for cancer patients.
Please find the scope of Dr.Seiffert’s studies in CLL tumor microenvironment at:https://www.dkfz.de/en/genetics/pages/projects/CLL/CLL-en.html
Host: Erbu Aydin
No registration required.
Welcome!
For more information about SAS-seminars: https://akademiliv.se/en/2020/06/66760/