Spatial transcriptomics reveal high T cell and monocyte status as predictive and prognostic markers in pancreatic cancer

Background: In the present study, we intended to discover predictive or prognostic factors of pancreatic ductal adenocarcinoma (PDAC). We intended to investigate the differences between PDAC cases that are treated with upfront surgery (UFS) and surgery after neoadjuvant FOLFIRINOX chemotherapy (NAT), and cases with good and poor responses to NAT, using digital spatial profiling (DSP) and immunohistochemical (IHC) analysis. Methods: Forty-eight PDAC cases that were surgically resected with or without NAT were included. A tissue microarray was constructed for DSP and IHC. Pathological tumor regression to NAT was graded based on the College of American Pathologists (CAP) system. Results: Between the UFS and NAT groups, there were no significant differentially expressed genes in all cell types. In the NAT group, MFAP4 and EGR3 were upregulated in CAP 2 in pan CK- and CD45-negative cells. Gene set enrichment analysis of CD45-positive cells showed that genes related to B or T cell-associated pathways were enriched in CAP 2, which correlated with the IHC; higher CD3-, CD4-, and CD8-positive cell densities in CAP 2. Multivariate analysis revealed age, high monocyte infiltration, and high CD68-positive cell infiltration as independent prognostic factors for overall survival. Conclusions: Increased expression of MFAP4 and EGR3 as well as high CD3-, CD4-, and CD8-positive cell infiltration may be predictive markers of the NAT response in PDAC. Additionally, high monocyte infiltration and high CD68-positive cell infiltration could serve as prognostic markers for PDAC.