To gain insight into immunological mechanisms of response and resistance to chemoimmunotherapy, we analyzed blood samples from patients (n=22) with advanced PDA treated with an anti-CD40 mAb (CP-870,893) in combination with gemcitabine. Patients with systemic inflammation, defined by neutrophil-lymphocyte ratio (NLR) >3.1, had a shorter median OS (5.8 vs 12.3mo; p=0.0105) as compared to patients with NLR <3.1. Taken together, our findings identify systemic inflammation as a potential resistance mechanism to a CD40-based chemoimmunotherapy and suggest biomarkers for future studies.