Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5371-5379 ◽  
Author(s):  
Camille Laurent ◽  
Sabina Müller ◽  
Catherine Do ◽  
Talal Al-Saati ◽  
Sophie Allart ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Lymph Nodes ◽  
Follicular Lymphoma ◽  
Imaging Study ◽  
Progression Free Survival ◽  
Tissue Imaging ◽  
Combined Chemotherapy ◽  
3 Dimensional

Abstract CD8+ CTLs are thought to play a role in the control of follicular lymphoma (FL). Yet, the link between CTL tissue distribution, activation status, ability to kill FL cells in vivo, and disease progression is still elusive. Pretreatment lymph nodes from FL patients were analyzed by IHC (n = 80) or by 3-color confocal microscopy (n = 10). IHC revealed a rich infiltrate of CD8+ granzyme B+ (GrzB) cells in FL interfollicular spaces. Accordingly, confocal microscopy showed an increased number of CD3+CD8+GrzB+ CTLs and a brighter GrzB staining in individual CTL in FL samples compared with reactive lymph nodes. CTLs did not penetrate tumor nodules. In 3-dimensional (3-D) image reconstructions, CTLs were detected at the FL follicle border where they formed lytic synapse-like structures with FL B cells and with apoptotic cells, suggesting an in situ cytotoxic function. Finally, although GrzB expression in CTLs did not correlate with risk factors, high GrzB content correlated with prolonged progression free-survival (PFS) after rituximab-combined chemotherapy. Our results show the recruitment of armed CTLs with a tumor-controlling potential into FL lymph nodes and suggest that CTL-associated GrzB expression could influence PFS in FL patients having received rituximab-combined chemotherapy.

scholarly journals Effectiveness of First-Line Management Strategies for Stage I Follicular Lymphoma: Analysis of the National LymphoCare Study

2012 ◽  
Vol 30 (27) ◽  
pp. 3368-3375 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Michelle Byrtek ◽  
Brian K. Link ◽  
Christopher Flowers ◽  
Michael Taylor ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Ct Scan ◽  
Systemic Therapy ◽  
Management Strategies ◽  
Imaging Study ◽  
Progression Free Survival ◽  
Stage I ◽  
Whole Body ◽  
Treatment Approaches ◽  
Positron Emission

PurposeThe optimal management of stage I follicular lymphoma, according to consensus guidelines, is based on uncontrolled experiences of select institutions. Diverse treatment approaches are used despite guidelines that recommend radiation therapy (XRT).Patients and MethodsWe analyzed outcomes of patients with stage I follicular lymphoma enrolled onto the National LymphoCare database.ResultsOf 471 patients with stage I follicular lymphoma, 206 patients underwent rigorous staging as defined by both a bone marrow aspirate and biopsy and an imaging study (a computed tomography [CT] scan of the whole body, a positron emission tomography [PET]/CT scan, or both). Rigorously staged patients had superior progression-free survival (PFS) compared with nonrigorously staged patients (hazard ratio [HR], 0.63). Treatments given to rigorously staged patients were rituximab/chemotherapy (R-chemo; 28%), XRT (27%), observation (17%), systemic therapy + XRT (13%), rituximab monotherapy (12%), and other (3%). With a median follow-up of 57 months for PFS, there were 44 progression events (in 21% of patients) for rigorously staged patients. For these patients, PFS was significantly improved with either R-chemo or systemic therapy + XRT compared with patients receiving XRT alone after adjustment for histology, LDH, and the presence of B symptoms. There were no differences in overall survival.ConclusionIn this largest, prospectively enrolled group of patients with stage I follicular lymphoma, variable treatment approaches resulted in similar excellent outcomes, which challenges the paradigm that XRT should be standard for this presentation.

Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with confocal microscopy

Ophthalmology ◽  
2001 ◽  
Vol 108 (10) ◽  
pp. 1744-1750 ◽  
Author(s):  
Pierre-Jean Pisella ◽  
Olivier Auzerie ◽  
Yves Bokobza ◽  
Caroline Debbasch ◽  
Christophe Baudouin
Keyword(s):  
Confocal Microscopy ◽  
Laser In Situ Keratomileusis

scholarly journals FORMULATION AND EVALUATION OF NOVEL IN SITU GEL OF LAFUTIDINE FOR GASTRO RETENTIVE DRUG DELIVERY

2018 ◽  
Vol 11 (8) ◽  
pp. 88
Author(s):  
Sindhoor S M ◽  
Sneh Priya ◽  
Amala Maxwell
Keyword(s):  
Drug Release ◽  
Imaging Study ◽  
Lag Time ◽  
In Vivo Studies ◽  
In Vitro Drug Release ◽  
In Situ Gel ◽  
Drug Content

Objective: The aim of the present study was to formulate and evaluate the novel in situ gel of lafutidine for gastroretentive drug deliveryMethods: A gastroretentive in situ gel of lafutidine was formulated by pH-triggered ionic gelation method using different concentrations of gelling polymer such as sodium alginate, gellan gum, and xanthum gum. Prepared formulations were evaluated for viscosity, density, buoyancy lag time and buoyancy duration, and drug content. In vitro drug release studies of all formulations were also performed. In vivo fluorescence imaging study was conducted for optimized formulation and compared with control.Results: The concentration of gelling agents and release retardant polymers significantly affected viscosity, floating behavior, and in vitro drug release of the formulations. The pH and drug content were found in the range of 6.72–7.20 and 88.74–95.33%, respectively. Floating lag time was <2 min; duration of floating was more than 12 h. Minimum and maximum in vitro drug release were found to be for formulation F9 (51.74%) and F1 (82.76%), respectively, at the end of 12 h. The drug was released from the all the formulations in a sustained manner. In vivo studies confirmed the gastroretention of the formulation in mice stomach for 8 h. Stability studies indicated that the there was no significant change in the visual appearance, floating behavior, and drug content.Conclusion: The gastroretentive in situ gel system, prolonged the gastric residence time, thereby targeting site-specific drug release in the upper gastrointestinal tract.

In vivo confocal microscopy through-focusing to measure corneal flap thickness after laser in situ keratomileusis

2002 ◽  
Vol 28 (6) ◽  
pp. 962-970 ◽  
Author(s):  
Fusun Gokmen ◽  
James V. Jester ◽  
Matthew W. Petroll ◽  
James P. McCulley ◽  
Dwight H. Cavanagh
Keyword(s):  
Confocal Microscopy ◽  
Laser In Situ Keratomileusis ◽  
In Vivo Confocal Microscopy ◽  
Flap Thickness

Surgical Margin Mapping of Melanoma In Situ Using In Vivo Reflectance Confocal Microscopy Mosaics

2021 ◽  
Vol 47 (5) ◽  
pp. 605-608
Author(s):  
John R. Durkin ◽  
Catherine N. Tchanque-Fossuo ◽  
Alexander N. Rose ◽  
Hillary R. Elwood ◽  
Shelly Stepenaskie ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Surgical Margin ◽  
Reflectance Confocal Microscopy ◽  
Melanoma In Situ

scholarly journals Tumor ablation plus co-administration of CpG and saponin adjuvants affects IL-1 production and multifunctional T cell numbers in tumor draining lymph nodes

2020 ◽  
Vol 8 (1) ◽  
pp. e000649
Author(s):  
Tonke K Raaijmakers ◽  
Renske J E van den Bijgaart ◽  
Martijn H den Brok ◽  
Melissa Wassink ◽  
Annemarie de Graaf ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Tumor Ablation ◽  
Polymorphonuclear Neutrophil ◽  
Cell Numbers ◽  
Draining Lymph Nodes

BackgroundTumor ablation techniques, like cryoablation, are successfully used in the clinic to treat tumors. The tumor debris remaining in situ after ablation is a major antigen depot, including neoantigens, which are presented by dendritic cells (DCs) in the draining lymph nodes to induce tumor-specific CD8+T cells. We have previously shown that co-administration of adjuvants is essential to evoke strong in vivo antitumor immunity and the induction of long-term memory. However, which adjuvants most effectively combine with in situ tumor ablation remains unclear.Methods and resultsHere, we show that simultaneous administration of cytidyl guanosyl (CpG) with saponin-based adjuvants following cryoablation affects multifunctional T-cell numbers and interleukin (IL)-1 induced polymorphonuclear neutrophil recruitment in the tumor draining lymph nodes, relative to either adjuvant alone. The combination of CpG and saponin-based adjuvants induces potent DC maturation (mainly CpG-mediated), antigen cross-presentation (mainly saponin-based adjuvant mediated), while excretion of IL-1β by DCs in vitro depends on the presence of both adjuvants. Most strikingly, CpG/saponin-based adjuvant exposed DCs potentiate antigen-specific T-cell proliferation resulting in multipotent T cells with increased capacity to produce interferon (IFN)γ, IL-2 and tumor necrosis factor-α in vitro. Also in vivo the CpG/saponin-based adjuvant combination plus cryoablation increased the numbers of tumor-specific CD8+T cells showing enhanced IFNγ production as compared with single adjuvant treatments.ConclusionsCollectively, these data indicate that co-injection of CpG with saponin-based adjuvants after cryoablation induces an increased amount of tumor-specific multifunctional T cells. The combination of saponin-based adjuvants with toll-like receptor 9 adjuvant CpG in a cryoablative setting therefore represents a promising in situ vaccination strategy.

scholarly journals Improved Induction of Anti-Melanoma T Cells by Adenovirus-5/3 Fiber Modification to Target Human DCs

Vaccines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 42 ◽  
Author(s):  
Dafni Chondronasiou ◽  
Tracy-Jane Eisden ◽  
Anita Stam ◽  
Qiana Matthews ◽  
Mert Icyuz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Targeted Delivery ◽  
Vaccination Strategy ◽  
Fiber Modification ◽  
Adenovirus 5 ◽  
In Vivo Delivery

To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8+ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. “Off-the-shelf” DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches.

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