The desmoplastic stroma of pancreatic cancer is a barrier to immune cell infiltration

Abstract

A detailed map demonstrating the spatially restricted distribution of immune cells within the desmoplastic stroma of human pancreatic tumors opens up the field of pancreatic oncoimmunology. CD8⁺ T cells located in the proximity of malignant lesions are associated with a survival advantage, suggesting the existence of immunoediting. Pancreatic stellate cells appear to dictate the infiltration of the juxtatumoral stroma by CD8⁺ T cells.

Keywords: B cells; CD8+ T cells; macrophages; natural killer cells; neutrophils.

Figure 1. Influence of ATRA on the immune cell subsets that infiltrate the stroma of pancreatic tumors. (A) The pancreatic ductal adenocarcinoma (PDAC) lesions developing in LSL-Kras^G12D/+-LSL-Trp53^R172H/+-Pdx-1-cre (KPC) mice exhibit the same pattern of infiltration by immune cells observed in human PDAC tissues. In particular, the distribution of neutrophils and macrophages is homogeneous throughout the stromal compartments, while regulatory T cells (Tregs), cytotoxic CD8⁺ T cells and B cells are enriched in the panstromal compartment compared with the juxtatumoral stroma. (B) The administration of all-trans retinoic acid (ATRA) to these mice induces the quiescence of pancreatic stellate cell, resulting in an increased proportion of cytotoxic T cells within the juxtatumoral stroma.