Organoids propagated from pancreatic cancer cells may provide a platform to study response to immune checkpoint inhibitors, according to a study presented at the AACR Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston, Massachuseetts.1
Though immune checkpoint inhibitors have been successful in many solid tumors, results with pancreatic ductal adenocarcinoma (PDAC) have been disappointing. The purpose of this study was to use PDAC organoids, which are microtumors created from cells harvested from patients during resection, to evaluate their immune reactivity and response to immune checkpoint inhibitors.
In the study, PDAC samples were collected from 8 patients undergoing pancreatic resection. Organoids were propagated and immune cells were isolated from the patients’ spleens during resection or from peripheral blood. The autologous immune cells were then co-cultured with the organoids to evaluate immune reactivity and response to an anti-PD-1 inhibitor.
The immune reactivity of the immune cells was mixed:some cells demonstrated reactivity when co-cultured with organoids and others were not reactive at all (compared with baseline). Immune reactivity was similar regardless of whether the immune cells were co-cultured with normal pancreatic organoids or organoids propagated from tumor cells.
Application of an anti-PD-L1 inhibitor increased the immune reactivity of immune cells to organoids derived from tumor cells, but not the immune reactivity to normal cells.
The authors concluded that these data demonstrate that “PDAC organoids may provide a platform to predict immune reactivity and efficacy of checkpoint blockade to guide individualized therapy.”
- Delrosario L, Lazarus J, Perusina-Lanfranca M, et al. Development of a personalized platform to predict immune reactivity and efficacy of immune checkpoint blockade in pancreas cancer. Presented at: AACR Pancreatic Cancer: Advances in Science and Clinical Care; Boston, Massachusetts: September 21-24, 2018. Abstract B003.