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SECRETORY LEUKOCYTE PROTEASE INHIBITOR: A NOVEL CANDIDATE FOR TUMOR IMMUNE EVASION MECHANISM IN PANCREATIC CANCER
REMOLINS CARLA; MATAMOROS KEVIN; LAMAS PAULA; VALENZUELA JOSE; GUERRIERI DIEGO; BOND OLIVIER; FRAUNHOFFER N; VANZINI DAMIAN ; FRATANTONI EUGENIA ; DI TULIO ORNELA ; KOHAN GUSTAVO ; ROMEO HORACIO; IOVANNA JUAN; CHULUYAN EDUARDO
Mar del Plata
Congreso; Reunión Conjunta SAIC SAI&FAIC SAFIS 2022; 2022
The immune surveillance failure reported in pancreatic ductal adenocarcinoma (PDAC) could be attributed to immune evasion factors (IEF) produced by cancer cells in the tumor microenvironment. We have described that secretory leukocyte protease inhibitor (SLPI) is an immunomodulator that downregulates the generation of monocyte- derived dendritic cells (moDCs), and it is produced by different PDAC tumor lines. However, it is not known if SLPI-producing PDAC affects the differentiation of monocytes to moDCs. The aim of the present work was to determine the effect of PDAC tumors on the generation of moCDs and the ability of these to produce SLPI. Samples of tumor and heparinized peripheral blood were obtained from patients bearing PDAC at the time of the surgical resection. Monocytes were isolated and cultured in differentiation medium (RPMI 1640, 10% FBS, 10 ng/ml IL-4, 36 ng/ml GMCSF, 1% penicillin- streptomycin) in the presence or absence of rhSLPI 320 ng/ml or co-culture with tumor explants (TE) in transwells. After 5 days, molecules CD14, CD1c and CD86 were measured by flow cytometry. Furthermore, the levels of SLPI in the plasma of the patients and in the tumor culture supernatants (TCS) were determined by ELISA. Plasma SLPI levels were detected in all patients but in only 4 out of 10 TCS. There was a tendency to impair CD1c expression by 81.8% (p= 0.0908; Kruskal-Wallis test) in SLPI-producing TE. In addition, there was a positive correlation between plasma levels of SLPI and the percentage of CD1c decrease in the co-culture (r=0.7702; p=0.0366). On the other hand, plasma levels of SLPI strongly correlated with the CD14/CD1c ratio detected in co-cultures (r= 0.94; p= 0.008). These results suggest that SLPI-producing PDAC contributes to the immunosuppressive microenvironment of pancreatic cancer by acting as an IEF and that its plasma levels could be an indicator of the state of the local immune response.