scholarly journals Infiltration of CD1a-Positive Dendritic Cells in Advanced Laryngeal Cancer Correlates with Unfavorable Outcomes Post-Laryngectomy

2020 ◽  
Author(s):  
Akimichi Minesaki ◽  
Keita Kai ◽  
Yuichiro Kuratomi ◽  
Shinichi Aishima
Keyword(s):  
Dendritic Cells ◽  
Clinical Outcomes ◽  
Laryngeal Cancer ◽  
Antitumor Immunity ◽  
Multivariate Analyses ◽  
Clinical Impact ◽  
High Group ◽  
Multidisciplinary Therapy ◽  
Unfavorable Clinical Outcome ◽  
Independent Unfavorable Prognostic Factor

Abstract Background: The prognosis of advanced laryngeal cancer is unfavorable despite the progress of multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer has not been clear.Patients and Methods: We retrospectively analyzed the cases of 57 patients with Stage Ⅲ or Ⅳ laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry for CD1a, S100, and CD8 was performed using representative resected specimens. CD1a+ DCs, S100+ DCs, and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and we divided the cases into high and low groups by the cut-off of the median value for each of these three parameters.Results: Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (p=0.0082) and overall survival (OS) (p=0.0324). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. Multivariate analyses indicated that the infiltration of CD1a+ DCs ​​​is an independent unfavorable prognostic factor in both DSS (p=0.0093) and OS (p=0.0132).Conclusions: Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes. It is not yet known why the presence of CD1a+ DCs lead to an unfavorable clinical outcome in laryngeal cancer. Further studies are necessary to validate our results and clarify the function(s) of tumor-infiltrating CD1a+ DCs.

scholarly journals Infiltration of CD1a-positive dendritic cells in advanced laryngeal cancer correlates with unfavorable outcomes post-laryngectomy

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Akimichi Minesaki ◽  
Keita Kai ◽  
Yuichiro Kuratomi ◽  
Shinichi Aishima
Keyword(s):  
Dendritic Cells ◽  
Clinical Outcomes ◽  
Laryngeal Cancer ◽  
Total Laryngectomy ◽  
Antitumor Immunity ◽  
Clinical Impact ◽  
High Group ◽  
Multidisciplinary Therapy ◽  
Independent Unfavorable Prognostic Factor ◽  
Disease Specific

Abstract Background The prognosis of advanced laryngeal cancer is unfavorable despite advances in multidisciplinary therapy. Dendritic cells (DCs) play a central role in antitumor immunity. Tumor-infiltrating CD1a+ DCs have been reported to be associated with clinical outcomes in carcinomas of various organs, but the clinical impact of CD1a+ DCs in laryngeal cancer remains to be unequivocally established. Methods We retrospectively analyzed the cases of 57 patients with Stage III or IV laryngeal cancer who underwent a total laryngectomy. Immunohistochemistry detection of CD1a, S100 and CD8 was performed on representative resected specimens. CD1a+ DCs, S100+ DCs and CD8+ cytotoxic T-lymphocytes (CTLs) were evaluated, and the cases divided into high and low groups according to the cut-off of the median values for each of these 3 parameters. Results Compared to the CD1a-low group, the CD1a-high group had more advanced cases and showed significantly worse disease-specific survival (DSS) (P = 0.008) and overall survival (OS) (P = 0.032). The analyses of S100 DCs and CD8+ CTLs revealed no significant impact on clinical outcomes. However, multivariate analysis revealed that infiltration of CD1a+ DCs was an independent unfavorable prognostic factor for both DSS (P = 0.009) and OS (P = 0.013). Conclusions Our results demonstrated that the infiltration of CD1a+ DCs was associated with unfavorable clinical outcomes in patients with advanced laryngeal cancer who underwent a total laryngectomy as the initial treatment.

scholarly journals Clinical Impact of Revised Ciprofloxacin Breakpoint in Patients with Urinary Tract Infections by Enterobacteriaceae

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 469
Author(s):  
Ga-Eun Park ◽  
Jae-Hoon Ko ◽  
Sun-Young Cho ◽  
Hee-Jae Huh ◽  
Jin-Yang Baek ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Clinical Outcomes ◽  
Urinary Tract Infections ◽  
Inhibitory Concentration ◽  
Clinical Impact ◽  
Definitive Treatment ◽  
Primary Endpoints ◽  
Tract Infections ◽  
Susceptible Group ◽  
Selection Of

In 2018, the Clinical and Laboratory Standards Institute (CLSI) revised ciprofloxacin (CIP)-susceptible breakpoint for Enterobacteriaceae from ≤1 μg/mL to ≤0.25 μg/mL, based on pharmacokinetic-pharmacodynamic (PK-PD) analysis. However, clinical data supporting the lowered CIP breakpoint are insufficient. This retrospective cohort study evaluated the clinical outcomes of patients with bacteremic urinary tract infections (UTIs) caused by Enterobacteriaceae, which were previously CIP-susceptible and changed to non-susceptible. Bacteremic UTIs caused by Enterobacteriaceae with CIP minimal inhibitory concentration (MIC) ≤ 1 μg/mL were screened, and then patients treated with CIP as a definitive treatment were finally included. Patients in CIP-non-susceptible group (MIC = 0.5 or 1 μg/mL) were compared with patients in CIP-susceptible group (MIC ≤ 0.25 μg/mL). Primary endpoints were recurrence of UTIs within 4 weeks and 90 days. A total of 334 patients were evaluated, including 282 of CIP-susceptible and 52 of CIP-non-susceptible. There were no significant differences in clinical outcomes between two groups. In multivariate analysis, CIP non-susceptibility was not associated with recurrence of UTIs. CIP non-susceptibility based on a revised CIP breakpoint, which was formerly susceptible, was not associated with poor clinical outcomes in bacteremic UTI patients were treated with CIP, similar to those of the susceptible group. Further evaluation is needed to guide the selection of definitive antibiotics for UTIs.

scholarly journals DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells

2021 ◽  
Vol 9 (5) ◽  
pp. e002054
Author(s):  
Francisco J Cueto ◽  
Carlos del Fresno ◽  
Paola Brandi ◽  
Alexis J. Combes ◽  
Elena Hernández-García ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Dendritic Cells ◽  
Tumor Growth ◽  
Antitumor Immunity ◽  
Elevated Serum ◽  
Dead Cell ◽  
Type I ◽  
Cross Presentation ◽  
Patients With Cancer ◽  
Deficient Mice

BackgroundConventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet.MethodsB16 and MC38 tumor cell lines were inoculated subcutaneously into wild-type (WT) and DNGR-1-deficient mice. To overexpress Flt3L systemically, we performed gene therapy through the hydrodynamic injection of an Flt3L-encoding plasmid. To characterize the immune response, we performed flow cytometry and RNA-Seq of tumor-infiltrating cDC1s.ResultsHere, we found that cross-presentation of tumor antigens in the steady state was DNGR-1-independent. However, on Flt3L systemic overexpression, tumor growth was delayed in DNGR-1-deficient mice compared with WT mice. Of note, this protection was recapitulated by anti-DNGR-1-blocking antibodies in mice following Flt3L gene therapy. This improved antitumor immunity was associated with Batf3-dependent enhanced accumulation of CD8+ T cells and cDC1s within tumors. Mechanistically, the deficiency in DNGR-1 boosted an Flt3L-induced specific inflammatory gene signature in cDC1s, including Ccl5 expression. Indeed, the increased infiltration of cDC1s within tumors and their protective effect rely on CCL5/CCR5 chemoattraction. Moreover, FLT3LG and CCL5 or CCR5 gene expression signatures correlate with an enhanced cDC1 signature and a favorable overall survival in patients with cancer. Notably, cyclophosphamide elevated serum Flt3L levels and, in combination with the absence of DNGR-1, synergized against tumor growth.ConclusionDNGR-1 limits the accumulation of tumor-infiltrating cDC1s promoted by Flt3L. Thus, DNGR-1 blockade may improve antitumor immunity in tumor therapy settings associated to high Flt3L expression.

Inhibition of topoisomerase I shapes antitumor immunity through the induction of monocyte-derived dendritic cells

2021 ◽  
Author(s):  
Jeong-Mi Lee ◽  
Kwang-Soo Shin ◽  
Choong-Hyun Koh ◽  
Boyeong Song ◽  
Insu Jeon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Topoisomerase I ◽  
Antitumor Immunity

PPARG-mediated ferroptosis in dendritic cells limits antitumor immunity

2021 ◽  
Author(s):  
Leng Han ◽  
Lulu Bai ◽  
Chunjing Qu ◽  
Enyong Dai ◽  
Jiao Liu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antitumor Immunity

Administration of interleukin-12 and -18 enhancing the antitumor immunity of genetically modified dendritic cells that had been pulsed with Semliki Forest virus—mediated tumor complementary DNA

2002 ◽  
Vol 97 (5) ◽  
pp. 1184-1190 ◽  
Author(s):  
Ryuya Yamanaka ◽  
Naoki Yajima ◽  
Naoto Tsuchiya ◽  
Junpei Honma ◽  
Ryuichi Tanaka ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antitumor Immunity ◽  
Semliki Forest Virus ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Antitumor Effects ◽  
Content Type ◽  
Immunogene Therapy ◽  
Fine Print

Object. Immunogene therapy for malignant gliomas was further investigated in this study to improve its therapeutic efficacy. Methods. Dendritic cells (DCs) were isolated from bone marrow and pulsed with phosphate-buffered saline or Semliki Forest virus (SFV)—mediated 203 glioma complementary (c)DNA with or without systemic administration of interleukin (IL)-12 and IL-18 to treat mice bearing the 203 glioma. To study the immune mechanisms involved in tumor regression, the authors investigated tumor growth of an implanted 203 glioma model in T cell subset—depleted mice and in interferon (IFN) γ—neutralized mice. To examine the protective immunity produced by tumor inoculation, a repeated challenge of 203 glioma cells was given by injecting the cells into the left thighs of surviving mice and the growth of these cells was monitored. The authors demonstrated that the combined administration of SFV-cDNA, IL-12, and IL-18 produced significant antitumor effects against the growth of murine glioma cells in vivo and also can induce specific antitumor immunity. The synergic effects of the combination of SFV-cDNA, IL-12, and IL-18 in vivo were also observed to coincide with markedly augmented IFNγ production. The antitumor effects of this combined therapy are mediated by CD4+ and CD8+ T cells and by NK cells. These results indicate that the use of IL-18 and IL-12 in DC-based immunotherapy for malignant glioma is beneficial. Conclusions. Immunogene therapy combined with DC therapy, IL-12, and IL-18 may be an excellent candidate in the development of a new treatment protocol. The self-replicating SFV system may therefore provide a novel approach for the treatment of malignant gliomas.

Association between HbA1C (glycated hemoglobin) and clinical outcomes in patients with subarachnoid hemorrhage after neuro-intervention

2021 ◽  
Vol 18 ◽  
Author(s):  
Chan Woong Park ◽  
Ho Jun Yi ◽  
Dong Hoon Lee ◽  
Jae Hoon Sung
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Glycated Hemoglobin ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Roc Curve Analysis ◽  
Optimal Cutoff ◽  
Cutoff Value ◽  
Unfavorable Clinical Outcome ◽  
High Hba1c

Objective: Our study investigated the association between level of HbA1c (glycated hemoglobin) at admission and the prognosis of aneurysmal subarachnoid hemorrhage (SAH). Methods: A total of 510 patients treated with neuro-intervention for aneurysmal SAH and with data for admission HbA1c (glycated hemoglobin) were included. Favorable clinical outcome was defined as Modified Rankin Scale (mRS) score of 0–2 at 3 months. Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff value of HbA1C for unfavorable clinical outcomes. Logistic regression was used to evaluate the association between HbA1C level and outcomes. Results: The optimal cutoff value of HbA1C was identified as 6.0% (P < 0.001), and patients with a high HbA1C (≥ 6.0%) had a lower prevalence of favorable clinical outcomes than patients with low HbA1C (< 6.0%) (P < 0.001). High HbA1C (≥ 6.0%) was independently associated with unfavorable clinical outcome (OR 2.84; 95% CI: 1.52-5.44; P = 0.004). The risk of unfavorable clinical outcome was significantly increased in patients with HbA1C (≥ 7.0%, < 8%) and HbA1C (≥ 8.0%) compared with lower baseline HbA1C (≥ 6.0%, < 7%) values (OR 2.17; 95% CI: 1.87-5.13; P = 0.011 and OR 4.25; 95% CI: 3.17-8.41; P = 0.005). Conclusions: Our study showed that HbA1C could be an independent predictor of worse outcome following neuro-intervention for aneurysmal SAH. High HbA1C (≥ 6.0%) was associated with unfavorable clinical outcome, and gradual elevation of HbA1C contributed to an increase in the risk of worse clinical outcome after SAH.

scholarly journals DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice

2013 ◽  
Vol 14 (1) ◽  
pp. 39 ◽  
Author(s):  
Jun Cao ◽  
Yiqi Jin ◽  
Wei Li ◽  
Bin Zhang ◽  
Yang He ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antitumor Immunity ◽  
Dna Vaccines
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