Wilms Tumor 1-Associated Protein Expression Is Linked to a T-Cell-Inflamed Phenotype in Pancreatic Cancer.

Background: The molecular driving forces of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDAC) remain unclear, which causing great difficulty in identifying an appropriate treatment strategy.

Aims: This study aims to explore the associations between expression of Wilms tumor 1-associated protein (WTAP) and effector T-cell infiltration in PDAC.

Methods: In this study, we explored the association between WTAP expression and infiltration level of CD8+ T cells in PDAC. 178 PDAC samples were selected from The Cancer Genome Atlas (TCGA) database. The associations between diverse immune-cell infiltration, Tumor Mutation Burden (TMB), immune checkpoints, and WTAP expression were performed via R software. Transcriptional hallmarks of anti-tumor immunity and known T-cell-inflamed signature of PDAC were both selected to explore the relevance to WTAP expression. Potential immune checkpoint blockade (ICB) response to different WTAP expression was predicted with tumor immune dysfunction and exclusion (TIDE) algorithm.

Results: WTAP was closely linked to CD8+ T-cell infiltration (r ≥ 0.5, P value < 0.05) and did not show notable association with TMB in PDAC. WTAP positively linked to T-cell-inflamed gene expression profiles (GEP) (IL2RB, IL2RA, ZAP70, ITK, CD3E, CD38, CD27, CD276, CD8A, CMKLR1, CXCR6, HLA-DQA1, HLA-DRB1, HLA-E, NKG7, and STAT1), cytolytic activity (GZMA and PRF1), various immune checkpoints (IDO1, CD274, HAVCR2, PDCD1, CTLA4, LAG3, and PDCD1LG2) and 4-chemokine signature (CCL4, CCL5, CXCL9, and CXCL10). Besides, increased expression of WTAP was related to a higher TIDE score.

Conclusions: WTAP marks PDAC tumors with an active anti-tumor phenotype and might help the identification of PDAC patients who might benefit from immunotherapies.