Immediate variations in high-dimensional circulating immune cells following pancreatectomy.

Objectives: Despite advancements in surgical techniques and perioperative care, pancreatic surgery remains a high-risk procedure with significant morbidity and mortality. Furthermore, understanding its impact on the immune system is essential for designing strategies that interact with it. The aim of this study was to elucidate the immunomodulation that occurs following pancreatectomy. Methods: Patients were recruited for the IMMUNOPANC trial (NCT03978702). We performed mass cytometry to analyse the circulating immune subpopulations and integrated the data using the hierarchical-stochastic neighbour embedding clustering analysis and Stabl algorithm. Results: Among the enrolled 39 patients, 33 (84.5%) had undergone pancreatectomy for neoplasia including 13 (39%) with pancreatic ductal adenocarcinoma. Twelve (32%) patients developed pancreatic fistula with a 90-day mortality rate of 2.5%. We phenotyped 156 samples and observed a significant increase in myeloid cells (26% vs. 34%, P = 0.018) after pancreatectomy. Natural killer cell proportions decreased on postoperative day one (POD1) compared with the preoperative levels (7% vs. 12%, P < 0.001). Similarly, both CD8+ and CD4+ T-cell proportions decreased significantly post-surgery (25% and 40%, respectively, P < 0.001). During a narrow window, we observed the alteration of NK cells, contraction of CD8+ T cells, and increase in the proportion of naive CD4+ T cells. These changes may be a result of the immune response to surgery but could also reflect lymphoid organ demargination. Conclusion: This study presents the first analysis of peripheral immune system trajectories following pancreatic surgery. Understanding these dynamics would facilitate the restoration of postoperative immunity, which is potentially crucial for recovery.