Abstract B063: Tertiary lymphoid organogenesis and lymphocyte activation in human organ chips

Abstract

Abstract The rates of tertiary lymphoid organ (TLO) formation in pancreatic cancer are very low but patients with TLO have dramatically better survival rates. Our goal is to understand how pancreatic cancer suppresses TLO so that we can improve patient survival and reduce recurrence. We integrated human cell lines from pancreatic and lung cancer with either high or low PDL1/L2 expression into our previously described lymphoid follicle (LF) chip (Goyal et al., Adv. Sci, 2022), where peripheral blood mononuclear cells are induced to form 3D TLO-like structures. The hot lung cancer cell line, which expressed high levels of PDL1/L2 and a “hot” phenotype in published murine studies, produced a high levels of cytokines and stimulated increased TLO formation in the LF chip. In contrast, the cold lung and pancreatic cell lines did not induce the cytokine signature or TLOs. Importantly, TLO formation correlated with increased B cell activation, anti-tumor CD8 activity and tumor cell death. We have coupled this in vitro study with analysis of the pancreatic cancer transcriptome from the Cancer Genome Atlas to identify therapeutic targets to promote TLO formation in pancreatic cancer. In ongoing studies, we are assessing the functionality of the lung cancer TLO in vitro and in vivo and identifying therapeutics that may improve TLO formation in pancreatic cancer. Citation Format: Yunhao Zhai, Pranav Prabhala, Lucas Barck, Min Wen Ku, Aditya Patil, Viktor Horvath, Russell A. Gould, Donald E. Ingber, Girija Goyal. Tertiary lymphoid organogenesis and lymphocyte activation in human organ chips [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B063.