Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment naïve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment naïve PDAC patients.
Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.
Higher baseline levels of the immunosuppressive cytokines IL-6 and IL-10 were strongly associated with poorer OS (p=0.008 and 0.026, respectively; HR=1.16 and 1.28, respectively), while higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (p=0.045; HR=0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO+) had longer OS (CD4 p=0.032; CD8 p=0.036; HR=0.36 and 0.61, respectively). While greater expression of the T cell checkpoint molecule CTLA-4 on CD8+ T cells was associated with significantly shorter OS (p=0.020; HR=1.53), the TIM3 molecule had a positive association with survival when expressed on CD4+ T cells (p=0.046; HR=0.62).
These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naïve metastatic PDAC patients to date.