To investigate the potential of pharmacological intervention using inhibitors of HPK1, we generated HPK1 kinase dead (KD) mice which carry a single loss-of-function point mutation in the kinase domain and interrogated the role of kinase activity in immune cells in the context of suppressive factors or the tumor microenvironment (TME).
HPK1 expression, axillary lymph node metastasis and tumor‑node‑metastasis (TNM) stage were identified as independent factors of overall survival (OS) in the ER‑positive group (P<0.05), and HPK1 positivity was associated with increased OS (P=0.048).
We found that loss of HPK1 protein expression correlated significantly with the progression of pancreatic intraepithelial neoplasias (P = 0.001) and development of invasive PDA.