膵癌術後患者におけるcirculating tumor DNA検出の意義

Background : Diffuse large B ‐ cell lymphoma (DLBCL) is aggressive and easy to relapse, and the potential to noninvasively monitor tumor evolutionary dynamics of DLBCL needs to be further established. Liquid biopsy has been proved a promising method to access tumor DNA through blood sample. In the current study the feasibility and clinicalsignificanceofcirculatingtumorDNA(ctDNA)for DLBCLwere assessed. Methods : A total of 19 tumor biopsy samples and 38 plasma samples from 40 de novo high ‐ intermediate/high ‐ risk DLBCL patients were evaluated at baseline. Longitudinal blood samples collected under chemotherapy were also collected. A targeted sequencing gene panel including 31 genes that are most frequently mutated in lymphoma was designed for this study. The gene mutation spectrum of DLBCL was analyzed via a recently developed methodology termed Circulating Single ‐ Molecule Amplification and Resequencing Technology (cSMART). Results : The median age of the patients was 59 years.Variants were identified in 32 (84%) patients. The mutation of genes detected with 10% or higher ratios include TP53 (42.1%), KMT2D (28.9%), CARD11 (21.1%), CREBBP (15.8%), B2M (15.8%), TNFAIP3 (15.8%), CD79B (13.2%), EP300 (13.2%), myc (10.5%), TRAF3(10.5%). Compared with the tumor tissue, ctDNA profiling showed good concordance (67.1%). MoremutationsitescouldbedetectedinctDNAthanthoseinmatched tumor tissue. ctDNA concentration at baseline was correlated with tumor burden, LDH and IPI score. In addition, patients with mutated TP53 and B2M before treatment predicted poor prognosis. Serial ctDNAanalysisshowed thatthe concentrationofctDNAhas utilityfor real ‐ time assessment of treatment response and increase of ctDNA level could predict progressive disease or clinical recurrence. Conclusion : Our results demonstrate that ctDNA analysis is a promising method for detection of mutation spectrum of DLBCL and disease surveillance during therapy. abstract. Background: Waldenström's macroglobulinemia (WM) is an incur-able low ‐ grade B ‐ cell Non ‐ Hodgkin lymphoma. WM resembles chronic lymphocytic leukemia (CLL) with regard to biologic Conclusion : These data represent the first systematic evaluation of the T ‐ cell compartment in WM. The qualitative and quantitative changes in the immune system seen in CLL are not found in WM; T ‐ cell numbers, distribution and functionality seem mostly preserved even in pretreated patients. These findings are encouraging for application of T ‐ cell directed immunotherapy in WM, especially for relapsed/refractory WM. not statistically different between EBV + and EBV ‐ patients (p > 0.05, MW test). However, when functional markers of CD4 + cells were evaluated, exclusively in EBV + cases, CD4 + cells positively correlated with GrB + cells (p = 0.008, r = 0.473, Spearman), whereas neither Foxp3 + nor Tbet + cells showed statistical correlation with CD4 + cells (p > 0.05, Spearman). CD4 + cells also displayed a statistical positive correlation with CD56 + cells, as marker of NK cells (p = 0.006, r = 0.488, Spearman), while, in contrast, in EBV ‐ cases a trend to a negative correlation was demonstrated between CD4 + and CD56 + cells (p = 0.06, r = ‐ 0.686, Spearman). Furthermore, CD56 + cells did not show a statistical correlation with GrB + cells (p > 0.05, Spearman). In addition, Tbet + cells correlated with Foxp3 + and GrB + cells (p = 0.001, r = 0.536; p = 0.04, r = 0.364, respec-tively) in EBV + cases whereas Foxp3 + cells correlated with GrB + cells (p = 0.013, r = 0.444, Spearman). All those correlations were not observed in EBV ‐ cases. None of the markers were associated with survival median used as cut off value (p > 0.05, long rank test). Conclusions : This study reflects that CD4 cells in the context of EBV ‐ associated pediatric HL may be involved in cytotoxic activity as observed in primary infection, and this activity could be direct, since NK cells were not correlated with cytotoxic GrB marker. In addition, this cytotoxic and proinflammatory activity of GrB + and Tbet + cells, respectively, may be counterbalanced by immunoregulatory Foxp3 + cells.