Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade

• DOI: 10.3389/fimmu.2024.1440530
• Publication Date: 2024-12-04T05:10:49Z
• Authors: Daniel A. Ruiz-To...; Jillian F. Wise; Brian Yinge Zhao; Joao Paulo Olivei...; Sara Cavallaro; Peter M. Sadow; Jacy Fang; Osman Yilmaz; Amar Patel; Christopher Loosb...; Moshe Sade-Feldman; Daniel L. Faden; Shannon L. Stott
• Keywords: Infiltration (HVAC); Immune Modulation

The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade have resulted various preclinical investigations, yet the mechanism action humans remains unknown. To decipher combinatory mode TLR8 and blockade, we employed a unique, open-label, phase 1b pre-operative window opportunity clinical trial (NCT03906526) head neck squamous cell carcinoma (HNSCC) patients. Matched pre- post-treatment tumor biopsies from same lesion were obtained. We used single-cell RNA sequencing custom multiplex staining to leverage unique advantage same-lesion longitudinal sampling. Patients receiving dual anti-PD-1 exhibited marked upregulation innate immune effector genes cytokines, highlighted by increased