G. Tushoski-Alemán1, K. Herremans1, S. Han1, S. Hughes1 1University Of Florida, Department Of Surgery, Gainesville, FL, USA
Introduction: Cytotoxic (CD8+) T-cells serve an essential role in the immune response to neoplasms. Assessment of intratumoral populations of CD8+ T-cells in pancreatic ductal adenocarcinoma (PDAC) have previously relied upon semi-quantitative assessment and remains largely unexplored in relation to overall survival. We hypothesized that CD8+ T-cell infiltration rates, measured quantitatively via a digital-pathology platform would associate with overall survival.
Methods: Fifty-five PDAC tumors and 28 non-malignant pancreatic tissues were assembled into a tissue microarray (TMA). TMA slides were immunohistochemically stained with anti-CD8 antibodies. Using the digital quantification software package (QuPath), we performed a quantitative measurement of the number of intratumoral CD8+ cells in PDAC. Overall survival analysis was performed using Kaplan-Meier method,
Results: CD8+ T-cells represented a mean of 2.22% of nucleated cells in PDAC tumors (Range 0.08% – 8.18%), while chronic pancreatitis samples had significantly fewer CD8+ cells (p=0.0001) with a mean of 0.80% (Range 0.07%-3.78%). Linear regression analysis of CD8+ cell percentages, splitting the cohort into 2 even groups at the median, revealed a correlation (R2=0.153, p=0.0032) between higher levels of CD8+ T-cells and overall survival. PDAC tumors with high levels of CD8+ cell infiltration were found to have significantly better survival than their CD8+ low level counterparts, with a median survival of 904 days compared to 237 days (p=0.0006).
Conclusion: We demonstrate that a quantitatively-determined percentage of tumor-infiltrating CD8+ T-cells in human PDAC significantly associates with superior survival in PDAC.