Stabilizing Tumor-Resident Mast Cells Restores T-Cell Infiltration and Sensitizes Sarcomas to PD-L1 Inhibition.

ABSTRACT:

Purpose

To explore the cellular cross-talk of tumor-resident mast cells (MC) in controlling the activity of cancer-associated fibroblasts (CAF) to overcome tumor microenvironment (TME) abnormalities, enhancing the efficacy of immune-checkpoint inhibitors in sarcoma.

Experimental design

We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurposed phase II cli

SUBMITTER: Panagi M 

PROVIDER: S-EPMC11145177 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature