Abstract
Background: Tumor microenvironment plays an important role in chemoresistance and tumor progression of PDAC. The role of tumor infiltrating lymphocytes in treated PDAC remains unclear. This study examines the distribution of intratumoral lymphocytes and their correlation with survival and clinicopathologic factors in patients with resected PDAC. Methods: We studied 75 patients who completed pancreaticoduodenectomy (PD) plus neoadjuvant therapies between 1999 and 2007. Neoadjuvant therapies included Gemcitabine + nab-paclitaxel and FOLFIRINOX or chemoradiation. Immunohistochemistry (IHC) for CD4, CD8, and FOXP3 were performed on resection specimens, which contained two representative slides from each patient. Digital images of IHC-stained slides were obtained at 20 x magnifications using a whole slide scanner (ScanScope, Aperio AT Turbo). Tumor regions were hand-annotated on whole slide images and computer assisted quantitative analysis was performed using Aperio’s ImageScope software. The tumor infiltrating lymphocytes were calculated as the percentage of positive staining area vs the total tumor area. Cox Regression analysis was performed for univariate and multivariate analysis. Results: The average percentage for CD4, CD8 positive cells were 6.08 ± 7.76, 2.84± 3.64, respectively in the treated cohort. Using the 50 percentile value as a cutoff, patients with high CD4+ lymphocytes had better disease free survival vs low CD4 positive lymphocytes (HR 0.234, P = 0.0031). There were no significant correlations between CD 4+, CD8+, CD68+, Granzyme B+, KP-1+, FOXP3+ lymphocytes and overall survival (p > 0.05). In multivariate analysis, neither CD4+ lymphocytes (HR: 0.49, P = 0.004), CD 8+ or CD 4/CD 8 ratio were independent prognostic factors for overall survival (See table).Table735PVariableUnivariate Analysis (DFS)Mulitivariate Analysis (DFS)P-valueHR (95% CI)P-valueHR (95% CI)CD 4 High vs. Low (Reference)0.0030.234 (0.073-0.627)0.5100.553 (0.094-3.220)CD 8 High vs. Low (Reference)0.0210.366 (0.146-0.858)0.6950.752 (0.170-2.919)CD 4/CD 8 ratio High vs. Low (Reference)0.0460.393 (0.141-0.983)0.1120.344 (0.084-1.281)CD 68/CD 4 ratio High vs. Low (Reference)0.0850.424 (0.123-1.114)0.2610.521 (0.135-1.561) Open table in a new tab Conclusions: Our study showed that the presence of high CD4+ and CD8+ lymphocytes is an independent prognostic factor for disease free survival in resectable neoadjuvant treated PDAC patients. We believe that neoadjuvant chemotherapy induces an enhanced immune response that may contribute to improved survival outcomes. Results are currently being analyzed looking at tumor infiltrating lymphocytes in resectable PDAC patients receiving receiving surgery alone. Legal entity responsible for the study: MD Anderson Cancer Center Funding: None Disclosure: All authors have declared no conflicts of interest.
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