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SUMMARY:Interplay between tissue tension and tumor immunity - Valerie Weav
 er\, Director of the Center for Bioengineering and Tissue Regeneration and
  Professor in the Department of Surgery\, UCSF\, USA
DTSTART:20211102T160000Z
DTEND:20211102T170000Z
UID:TALK165277@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Tumors show increased tissue level force and present with a re
 modeled\, stiffened extracellular matrix (ECM). Moreover\, transformed cel
 ls exhibit a perturbed oncogene-stimulated and ECM-tuned mechanophenotype 
 that further stimulates ECM remodeling and stiffening. My group has been e
 xploring how the aberrant cell and tissue level forces arise and by what m
 eans they contribute to malignancy and metastasis\, as well as tumor recur
 rence and treatment resistance. We use two and three dimensional culture m
 odels with tuned ECM stiffness\, as well as transgenic and syngeneic mouse
  models\, human PDX models and human biospecimens\, in which ECM crosslink
 ing and stiffness and integrin mechanosignaling are manipulated and quanti
 fied. Our work has thus far revealed that the tumor ECM is progressively r
 emodeled\, and stiffened\, primarily by stromal fibroblasts prior to malig
 nant transformation. We determined that infiltrating pro-tumorigenic myelo
 id cells secrete factors that stimulate stromal fibroblasts to remodel and
  crosslink the ECM very early during tumor evolution. The stromal-fibrobla
 st stiffened ECM thereafter disrupts tissue organization\, promotes cell g
 rowth and survival and drives cell invasion. The stiffened tumor stroma ad
 ditionally drives angiogenesis\, and activates STAT3 to increase expressio
 n of cytokines and chemokines that stimulate immune cell infiltration. The
  stiffened ECM thereafter differentially modulates TGF signaling in the
  myeloid cells to alter their metabolism and drive their synthetic ECM phe
 notype that accelerates tumor aggression and metastatic dissemination by i
 mpairing CD8 T cell anti-tumor immunity. During my presentation I will dis
 cuss the dynamic and reciprocal interplay between tissue tension and innat
 e and acquired immunity\, and how this forces tumor aggression and metasta
 sis. 
LOCATION:Zoom: https://mrc-lmb-cam-ac-uk.zoom.us/j/92866604568?pwd=TlljTHk
 5VGEzd2YzM3JHQkxOaWdRUT09
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