scholarly journals Peripheral Helper Lymphocytes Produce Interleukin 12 in Cancer Patients

2013 ◽  
Vol 7 ◽  
pp. CMO.S11292 ◽  
Author(s):  
Márcia A. Michelin ◽  
Douglas R. Abdalla ◽  
Andréa A.R. Aleixo ◽  
Eddie F.C. Murta
Keyword(s):  
T Lymphocytes ◽  
Cancer Patients ◽  
Ex Vivo ◽  
Interleukin 12 ◽  
T Helper ◽  
Spleen Cells ◽  
Healthy Donors ◽  
Chronic Disease State

The aim of the study was to seek evidence for the production of IL-12 by CD4+ T lymphocytes in in vitro and ex vivo trials. We performed in vitro trials with spleen cells from mice subjected to carcinogenesis, as well as ex vivo trials with cells obtained from the peripheral blood of healthy individuals and cancer patients. We were able to verify a significantly increased expression of IL-12 in CD4+ T lymphocytes from mice and patients with tumors, compared to controls. Follow-up studies are needed to clarify whether this difference is related to being in a chronic disease state or whether it is an attempt by the immune system to produce an anti-tumor response, since T lymphocytes from healthy donors were not able to produce IL-12 when in contact with polyclonal stimuli. We concluded that, in cancer, T helper cells are capable of synthesizing IL-12, raising the question of whether we are faced with another profile, Th12.

scholarly journals Role of Dendritic Cells in the Pathogenesis of Whipple's Disease

2014 ◽  
Vol 83 (2) ◽  
pp. 482-491 ◽  
Author(s):  
Katina Schinnerling ◽  
Anika Geelhaar-Karsch ◽  
Kristina Allers ◽  
Julian Friebel ◽  
Kristina Conrad ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Interleukin 12 ◽  
Lymphoid Tissues ◽  
Whipple’S Disease ◽  
Whipple's Disease ◽  
Content Type ◽  
Healthy Donors ◽  
Stimulatory Capacity

Accumulation ofTropheryma whipplei-stuffed macrophages in the duodenum, impairedT. whipplei-specific Th1 responses, and weak secretion of interleukin-12 (IL-12) are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution, and functionality of DCex vivoor afterin vitromaturation by fluorescence-activated cell sorting (FACS) and by immunohistochemistryin situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11chighmyeloid DC (M-DC). Decreased maturation markers CD83, CD86, and CCR7, as well as low IL-12 production in response to stimulation, disclosed an immature M-DC phenotype.In vitro-generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under proinflammatory conditions but produced less IL-12 and failed to activateT. whipplei-specific Th1 cells. In duodenal and lymphoid tissues,T. whippleiwas found within immature DC-SIGN+DC. DC and proliferating lymphocytes were reduced in lymph nodes of CWD patients compared to levels in controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming ofT. whipplei-specific T cells during CWD and that immature DC carryingT. whippleicontribute to the dissemination of the bacterium.

O-062 In vitro maturation of oocytes in connection with ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M De Vos
Keyword(s):  
Cancer Patients ◽  
In Vitro Maturation ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Tissue Processing ◽  
Novel Approach ◽  
Tissue Cryopreservation

Abstract Abstract text Discussing fertility preservation (FP) in young cancer patients has become a key component of routine oncological health care. Although ovarian stimulation followed by oocyte cryopreservation has been recommended in cases where two to three weeks are available before the start of chemotherapy, ovarian tissue cryopreservation (OTC) is the preferred option when this timeframe is not available and when the potential gonadotoxic impact of cancer therapy is deemed moderate or severe, or in prepubertal girls. During ovarian tissue processing in the laboratory, cumulus-oocyte complexes can be identified. In vitro maturation and further vitrification of oocytes retrieved in ex vivo from the extracted ovarian tissue (ovarian tissue oocytes in vitro maturation; OTO-IVM) can be attempted to enhance the future reproductive options of the patient. Although the number of reported live births after OTO-IVM are limited, this experimental FP procedure has potential to become a standard appended procedure in conjunction with OTC. In cancer patients with haematological tumours and ovarian invasion, or patients with primary tumours of the ovary, ovarian tissue grafting may be contraindicated because of the risk of reintroducing malignant cells. Utilisation of vitrified oocytes after OTO-IVM may be the only hope for genetic offspring for these patients. Moreover, exogenous hormonal pretreatment is not required and COC can be recovered during ovarian tissue processing in the majority of patients who undergo partial or total unilateral oophorectomy. Nevertheless, maturation rates after OTO-IVM vary and are generally lower compared to IVM of transvaginally harvested IVM oocytes; currently available IVM systems registered for clinical use will have to be adapted to accommodate the in vitro requirements of oocytes derived from extracorporeal ovarian tissue, and follow-up data are needed to assess the success rate and safety of this novel approach.

scholarly journals Data Driven Mathematical Model of FOLFIRI Treatment for Colon Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2632
Author(s):  
Aparajita Budithi ◽  
Sumeyye Su ◽  
Arkadz Kirshtein ◽  
Leili Shahriyari
Keyword(s):  
Mathematical Model ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Immune Cell ◽  
Treatment Options ◽  
Data Driven ◽  
T Helper ◽  
Primary Tumors ◽  
Cell Fractions

Many colon cancer patients show resistance to their treatments. Therefore, it is important to consider unique characteristic of each tumor to find the best treatment options for each patient. In this study, we develop a data driven mathematical model for interaction between the tumor microenvironment and FOLFIRI drug agents in colon cancer. Patients are divided into five distinct clusters based on their estimated immune cell fractions obtained from their primary tumors’ gene expression data. We then analyze the effects of drugs on cancer cells and immune cells in each group, and we observe different responses to the FOLFIRI drugs between patients in different immune groups. For instance, patients in cluster 3 with the highest T-reg/T-helper ratio respond better to the FOLFIRI treatment, while patients in cluster 2 with the lowest T-reg/T-helper ratio resist the treatment. Moreover, we use ROC curve to validate the model using the tumor status of the patients at their follow up, and the model predicts well for the earlier follow up days.

scholarly journals Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones.

1994 ◽  
Vol 179 (4) ◽  
pp. 1273-1283 ◽  
Author(s):  
R Manetti ◽  
F Gerosa ◽  
M G Giudizi ◽  
R Biagiotti ◽  
P Parronchi ◽  
...  
Keyword(s):  
T Cells ◽  
Interferon Gamma ◽  
Specific Antigen ◽  
Th2 Cells ◽  
Interleukin 12 ◽  
T Helper ◽  
Ifn Gamma ◽  
Selection Of

Interleukin 12 (IL-12) facilitates the generation of a T helper type 1 (Th1) response, with high interferon gamma (IFN-gamma) production, while inhibiting the generation of IL-4-producing Th2 cells in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4+ and CD8+ clones with the ability to produce IFN-gamma at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-gamma production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4+ and some of the CD8+ clones produced variable amounts of IL-4. Unlike IFN-gamma, IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the clone progenitors, inducing their differentiation to high IFN-gamma-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this clonal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-gamma with any other inducer did produce IFN-gamma at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-gamma gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-gamma producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-gamma production or with only a transient low level expression of the IFN-gamma gene, depending on their stage of differentiation.

scholarly journals Interleukin-12 Is the Optimum Cytokine To Expand Human Th17 Cells In Vitro

2009 ◽  
Vol 16 (6) ◽  
pp. 798-805 ◽  
Author(s):  
Soad Nady ◽  
James Ignatz-Hoover ◽  
Mohamed T. Shata
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Interleukin 12 ◽  
Interleukin 17 ◽  
Functional Evaluation ◽  
Optimum Conditions ◽  
T Helper ◽  
Ifn Γ

ABSTRACT Recently, a new lineage of CD4+ T cells in humans and in mice has been reported. This T helper cell secretes interleukin-17 (IL-17) and has been defined as T helper 17 (Th17). Th17 cells express the IL-23 receptor (IL-23R) and play an important pathogenic role in different inflammatory conditions. In this study, our aim was to characterize the optimum conditions for isolation and propagation of human peripheral blood Th17 cells in vitro and the optimum conditions for isolation of Th17 clones. To isolate Th17 cells, two steps were taken. Initially, we negatively isolated CD4+ T cells from peripheral blood mononuclear cells of a normal human blood donor. Then, we isolated the IL-23R+ cells from the CD4+ T cells. Functional studies revealed that CD4+ IL-23R+ cells could be stimulated ex vivo with anti-CD3/CD28 to secrete both IL-17 and gamma interferon (IFN-γ). Furthermore, we expanded the CD4+ IL-23R+ cells for 1 week in the presence of anti-CD3/CD28, irradiated autologous feeder cells, and different cytokines. Our data indicate that cytokine treatment increased the number of propagated cells 14- to 99-fold. Functional evaluation of the expanded number of CD4+ IL-23R+ cells in the presence of different cytokines with anti-CD3/CD28 revealed that all cytokines used (IL-2, IL-7, IL-12, IL-15, and IL-23) increased the amount of IFN-γ secreted by IL-23R+ CD4+ cells at different levels. Our results indicate that IL-7 plus IL-12 was the optimum combination of cytokines for the expansion of IL-23R+ CD4+ cells and the secretion of IFN-γ, while IL-12 preferentially stimulated these cells to secrete predominately IL-17.

scholarly journals Vγ9Vδ2 T cells as a promising innovative tool for immunotherapy of hematologic malignancies

2011 ◽  
Vol 4 (4) ◽  
pp. 211
Author(s):  
Serena Meraviglia ◽  
Carmela La Mendola ◽  
Valentina Orlando ◽  
Francesco Scarpa ◽  
Giuseppe Cicero ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
Hematologic Malignancies ◽  
Cytolytic Activity ◽  
Cell Therapies ◽  
Stressed Cells

The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.<br />

scholarly journals Primary generation of cytolytic T lymphocytes in the absence of DNA synthesis.

1979 ◽  
Vol 150 (1) ◽  
pp. 196-201 ◽  
Author(s):  
H R MacDonald ◽  
R K Less
Keyword(s):  
T Lymphocytes ◽  
Dna Synthesis ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Spleen Cells ◽  
Con A ◽  
A Cell ◽  
Stimulation Of

The requirement for DNA synthesis during the primary differentiation of cytolytic T lymphocytes (CTL) had been investigated. CTL were induced polyclonally in vitro by stimulation of normal C57BL/6 spleen cells with concanavalin A (Con A)and their cytolytic activity was tested against 51Cr-labeled target cells in the presence of Bacto Phytohemagglutinin M. With this system, CTL activity could first be detected 48 h after exposure of spleen cells to Con A. Addition of cytosine arabinoside at concentrations sufficient to reduce DNA synthesis by 95-98% in Con A-stimulated cultures did not significantly inhibit the generation of cytolytic activity on a cell-to-cell basis. These results demonstrate that derepression of the genetic information required for the expression of CTL function can occur in the absence of detectable DNA synthesis.

Fibronectin maintains survival of mouse natural killer (NK) cells via CD11b/Src/β-catenin pathway

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4081-4088 ◽  
Author(s):  
Ting Zhang ◽  
Shuxun Liu ◽  
Pengyuan Yang ◽  
Chaofeng Han ◽  
Jianli Wang ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nuclear Translocation ◽  
Nk Cell ◽  
Ex Vivo ◽  
Interleukin 12 ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
B Cell Leukemia

Abstract Tissue microenvironment and stroma-derived extracellular matrix (ECM) molecules play important roles in the survival and differentiation of cells. Mouse natural killer (NK) cells usually die within 24 hours once isolated ex vivo. Exogenous cytokines such as interleukin-12 (IL-12) and IL-15 are required to maintain the survival and activity of mouse NK cells cultured in vitro. Whether and how ECM molecules such as fibronectin can support the survival of NK cells remain unknown. We demonstrate that fibronectin, just like IL-15, can maintain survival of mouse NK cells in vitro. Furthermore, we show that fibronectin binds to the CD11b on NK cells, and then CD11b recruits and activates Src. Src can directly interact with β-catenin and trigger nuclear translocation of β-catenin. The activation of β-catenin promotes extracellular signal-related kinase (ERK) phosphorylation, resulting in the increased expression of antiapoptotic protein B-cell leukemia 2 (Bcl-2), which may contribute to the maintenance of NK-cell survival. Consistently, fibronectin cannot maintain the survival of CD11b− NK cells and β-catenin–deficient NK cells in vitro, and the number of NK cells is dramatically decreased in the β-catenin–deficient mice. Therefore, fibronectin can maintain survival of mouse NK cells by activating ERK and up-regulating Bcl-2 expression via CD11b/Src/β-catenin pathway.

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