Looking deeper at SPP1 we found increased expression is associated with broad remodeling of the myeloid compartment – including emergent immunosuppressive phenotypes, a changed metabolic profile, and a reduction in inflammatory IL/IFN signaling
Comments
Log in with your Bluesky account to leave a comment
To extend these findings to other solid tumors we turned to an IFN deficient JAK1-knockout mouse model of melanoma. In this model we also found an immunosuppressive myeloid cell population emergent in the IFN deficient mice but not the WT tumors.
Mimicking results from our human studies, the JAK1 KO model showed striking resistance to CAR T therapy. Again, SPP1 signaling was a dominant feature of the TME signaling in these tumors.
Finally, we demonstrate that blocking SPP1 in the JAK1 KO model and a mouse glioma model resulted in dramatic therapeutic improvement and broad remodeling of the suppressive TME. We are excited to push this work forward and work to improve outcomes for patients with solid tumors.
This is the product of a fantastic collaboration, building on 8 years of work w/ Christine Brown. However, the true superstars of this study are @heinimnatri.bsky.social from my group and Sherri Gholamin from Christine’s. They did an amazing job leading this study and I’m so proud of the work.
Comments