Neoadjuvant PD-L1/TGFβ Blockade Can Rapidly Disrupt the Tumor Stroma in Head and Neck Cancer Patients

ABSTRACT: TGFβ drives fibroblast activation in cancer and is a resistance biomarker to PD-1/PD-L1 blockade. Focusing on the tumor stroma, we characterized the impact of neoadjuvant treatment with bintrafusp-alfa (BA), a dual PD-L1 and TGFβ inhibitor, in a window-of-opportunity study with six head and neck squamous cell carcinoma (HNSCC) patients. Tumor biopsies pre-treatment and 3-weeks post-therapy were analyzed using single-cell RNA sequencing, imaging and spatial transcriptomics. After treatment, we observed significant decreased levels of activated LRRC15+ cancer-associated fibroblasts (CAF); remodeled stromal architecture with reduced collagen I and XII content; and increased CD8+ T-cell infiltration in immune-excluded tumors. These changes were independently confirmed in an additional neoadjuv

SUBMITTER: Caroline Hoffmann 

PROVIDER: S-BIAD4011 | bioimages |

REPOSITORIES: bioimages