cDC1 dysregulation in cancer: An opportunity for intervention

Abstract

Conventional dendritic cells driven by the transcription factor Batf3 (cDC1 cells) are critical for the activation and maintenance of tumor-specific CD8+ T cells. In this issue of JEM, Lin et al. (https://doi.org/10.1084/jem.20190673) demonstrate systemic dysfunction of cDC1 cells in pancreatic cancer, which offers potential treatment strategies to expand the benefit of checkpoint blockade immunotherapy.

Insights from Thomas F. Gajewski and Kyle R. Cron.

PDA has systemic effects on DC function as described by Lin et al. (2020). Production of IL-6 by PDA causes a decrease in DC survival as well as function (left). Blockade of IL-6 via intraperitoneal injection of an IL-6–depleting antibody causes a global restoration of DC survival (middle). Treatment using Flt3L and anti-CD40 agonist results in improved systemic DC survival and function as measured by CD80, CD86, and MHC-II. It also results in infiltration of PDA tumors by DCs, as well as CD8 T cells and an overall reduction in tumor burden (right).