Abstract Title: Characterization of Natural Killer and Cytotoxic T Cell Immune Infiltrates in Pancreatic Ductal Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis and resistance to systemic therapies including immunotherapy. Although PDAC has been linked to low T cell infiltrate, the contribution of natural killer (NK) cells has received less attention. Our objective was to evaluate the immune parameters PDAC, including markers of NK cells, to determine if NK cells associate with patient outcomes. 

Methods: We analyzed tumors from 93 PDAC patients treated from 2012 – 2020. Predictor variables included tumor infiltrating lymphocytes (TILs), T cell markers (CD3+, CD8+, CD45RO+), NK markers (NKp46) and NK inhibitory markers (TIGIT and MHC-I). TILs were scored from 0-3, and immune markers were scored from 0-300. We also evaluated neutrophil and lymphocyte levels in the blood. Primary outcome variables were metastasis-free survival (MFS) and overall survival (OS), analyzed by the Kaplan-Meier method. 


Results: Mean age was 70, 55% were female, and the mean tumor size was 3.1±1.1cm. 89% involved the pancreatic head, and 63% were lymph node positive. The majority of patients received adjuvant therapy. With a median follow up of 24 months, median survival was 35 months. Blood lymphocytes levels prior to surgery were positively correlated with TILs (p=0.008 r=0.3). Median TILs infiltration was 1.1, and 50% were 0 or 1. Mean CD3+ score was 20.6±1, and mean NKp46 was 3.1±3.9. Although there was slight positive correlation between T cell and NK cell scores (CD3+/NKp46 p=0.005, r=0.3; CD8+/NKp46 p=0.05, r=0.2), neither T nor NK cell infiltration was associated with MFS or OS. Similarly, there was a tight positive correlation between MHC-I expression and all T cell markers (CD3+, CD8+ and CD45RO+), but not with NKp46 nor with survival outcomes (MFS/OS, P>0.05). TIGIT expression was also low (mean 30.8±21.9).

Conclusion: NK and T cell infiltrates are overall low in PDAC and do not associate with oncologic outcomes. Further characterization of the immune infiltrate in PDAC, including inhibitory signals and suppressive cell types, may yield better biomarkers of prognosis and immune targeting in this refractory disease.


Julia Persky

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