DC-1

Objectives:CellaVision DC-1 (DC-1, Sysmex, Kobe, Japan) is a newly launched digital morphology analyzer that was developed mainly for small to medium-volume laboratories. We evaluated the precision, qualitative performance, comparison of cell counts between DC-1 and manual counting, and turnaround time (TAT) of DC-1.Methods:Using five peripheral blood smear (PBS) slides spanning normal white blood cell (WBC) range, precision and qualitative performance of DC-1 were evaluated according to the Clinical and Laboratory Standards Institute (CLSI) EP15-A3, EP15-Ed3-IG1, and EP12-A2 guidelines. Cell counts of DC-1 and manual counting were compared according to the CLSI EP 09C-ED3 guidelines, and TAT of DC-1 was also compared with TAT of manual counting.Results:DC-1 showed excellent precision (%CV, 0.0-3.5%), high specificity (98.9-100.0%), and high negative predictive value (98.4-100.0%) in 18 cell classes (12 WBC classes and six non-WBC classes). However, DC-1 showed 0% of positive predictive value in seven cell classes (metamyelocytes, myelocytes, promyelocytes, blasts, plasma cells, nucleated red blood cells, and unidentified). The largest absolute mean differences (%) of DC-1 vs. manual counting was 2.74. Total TAT (min:s) was comparable between DC-1 (8:55) and manual counting (8:55).Conclusions:This is the first study that comprehensively evaluated the performance of DC-1 including its TAT. DC-1 has a reliable performance that can be used in small to medium-volume laboratories for assisting PBS review. However, DC-1 may make unnecessary workload for cell verification in some cell classes.

The tissue distribution and the ontogeny of DC-1 antigens have been investigated and compared with those of HLA-DR antigens. Indirect immunofluorescence (IIF) staining of surgically removed normal tissues from adults with the monoclonal antibody (MoAb) BT3.4 has detected DC-1 antigens in tissues of various embryologic origin. The tissue distribution of DC-1 antigens is more restricted than that of HLA-DR antigens, as the former are not detected in duodenal epithelium, colon mucosa, and ductal mammary gland epithelium. In fetuses up to 26 weeks of age, DC-1 antigens were detected only on cortical and medullary thymic dendritic cells with an anatomic distribution similar to that of reticuloepithelial cells and in endothelial cells of the small intestine. At this stage of intrauterine life, HLA-DR antigens have already reached their full tissue distribution. The tissue distribution and the ontogeny of DC-1 antigens resemble those of their murine counterparts, i.e., the I-A antigens.

The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL-G12D/+Tp53fl/fl(KP) and the KrasLSL-G12D/+Lkb1fl/fl(KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+and CD4+T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.