Comparative Immune profiling in Pancreatic Ductal Adenocarcinoma Progression Among South African patients

Abstract

Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate of only 11%. PDAC is characterized by an immunosuppressive microenvironment; thus, there have been multiple attempts to target it, although with little success. A better understanding of the immune landscape in PDAC is required to help elucidate the roles of these cells for effective targeting. This study investigated the expression of circulating key immune cell markers in South African PDAC patients. Method: Blood samples were obtained from a total of 34 PDAC patients consisting of 22 resectable (RPC), 8 locally advanced (LAPC) and 4 metastatic (MPC), 6 Chronic Pancreatitis (CP), and 6 healthy volunteers (HC). Immunophenotyping, real-time polymerase chain reactions (PCR), enzyme-linked immunosorbent assay (Elisa), and reactive oxygen species (ROS) assays were conducted. Statistical analysis was conducted in R (version 3.6.1) and Wilcoxon and Kruskal-Wallis rank-sum tests were used to compare between groups. Kaplan-Meier analysis and Spearman's rank test were used for survival and correlation analyses, respectively. Results: Granulocyte and neutrophil levels were significantly elevated while lymphocytes decreased with PDAC severity. The total percentages of CD4+, CD8+, and CD3+CD4-CD8- T-cells increased across the group. Of note are the reduction of CD16+ NKTs across the RPC (p = 0.002), LAPC (p = 0.01), and MPC (p = 0.017) groups when compared to HC. Both NK (p = 0.0047) and NKTs (p = 0.0027) increased in RPC but decreased in both LAPC and MPC when compared to HC. Although there was no statistical correlation or differences observed when comparing the PDAC groups with the control groups, RPC had the highest foldchange for both CD4 and CD3 while the LAPC group had the highest fold change for CD8 and CD16 genes compared to MPC. The inflammatory status of PDAC was assessed by DEPPD levels of serum which were elevated in RPC (p = 0.003) and LAPC (p = 0.008) but decreased in MPC (p = 0.025), compared to the HC group. ROS was shown to be positively correlated with GlycA (R=0.45, p = 0.00096). Conclusion: The expression of these immune cell markers observed in this pilot study provides insight into their potential roles in tumour progression in the patient group and suggests their potential utility in the development of immunotherapeutic strategies.