Multivariate statistical data analysis as a tool to analyze ex vivo expansion dynamics of cytokine-induced killer cells

Zanon, Cristina; Stocchero, Matteo; Albiero, Elena; Castegnaro, Silvia; Chieregato, Katia; Madeo, Domenico; Rodeghiero, Francesco; Astori, Giuseppe

doi:10.1002/cyto.b.21124

Cited by 7 publications

(4 citation statements)

References 17 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CIK cells consist of CD3 + CD56 + double positive and NK cells, and CD3 + CD56 -T lymphocytes. The antitumor activity of CIK cells seems to be associated with the CD3 + CD56 + subset, which has an in vitro fold expansion that varies from a few to >1,000-fold (24). The reason for this variability is unclear, and additional strategies are currently under investigation to improve the expansion rates.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood

et al. 2014

View full text Add to dashboard Cite

Cord blood has gradually become an important source for hematopoietic stem cell transplantation (HSCT) in the human, particularly in pediatric patients. Adoptive cellular immunotherapy of patients with hematologic malignancies after umbilical cord blood transplant is crucial. Cytokine‑induced killer (CIK) cells derived from cord blood are a new type of antitumor immune effector cells in tumor prevention and treatment and have increasingly attracted the attention of researchers. On the other hand, it has been suggested that preterm infant cord blood retains an early differentiation phenotype suitable for immunotherapy. Therefore, we determined the phenotypic and functional characterization of CIK cells derived from preterm infant cord blood (PCB-CIK) compared with CIK cells from term infant cord blood (TCB-CIK). Twenty cord blood samples were collected and classified into two groups based on gestational age. Cord blood mononuclear cells (CBMCs) were isolated, cultured and induced to CIK cells in vitro. We used flow cytometry to detect cell surface markers, FlowJo software to analyze the proliferation profile and intracellular staining to test the secretion of cytokines. Finally, we evaluated the antitumor activity of CIK cells against K562 in vitro. Compared with TCB-CIK, PCB-CIK cells demonstrated faster proliferation and higher expression of activated cell surface markers. The secretion of IL-10 was lower in PCB-CIK cells while the expression of perforin and CD107a had no significant difference between the two cell groups. PCB-CIK cells exhibited a high proliferation rate while the cytotoxic activity had no difference between the PCB-CIK and TCB-CIK cells. Hence preterm infant cord blood may be a potential source for immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The combination of these two pathways can effectively inhibit tumor growth and proliferation, in addition to aiding the body in its recovery of immune functions, thereby reducing residual tumor cell numbers as much as possible. As a more advanced and effective method than those previously employed, DC-CIK can significantly improve patient life quality and extend survival time, and has received satisfactory clinical efficacy reviews (Zhang et al, 2012;Zeng et al, 2013;Zanon et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on survival rate and in vitro immune response

Fang¹,

Jiang²,

Xia³

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of this study was to investigate the effects of dendritic cell (DC) therapy in osteosarcoma. Bone marrow DCs from Wistar (allograft group) and Sprague Dawley (SD) (homograft group) rats were electrically fused with the SD-derived osteosarcoma cell line UMR106 to generate a DC-osteosarcoma fusion (DOF) tumor vaccine, which was co-incubated with SD T lymphocytes to stimulate T cell proliferation. CD8+ and CD4+ cell percentages were measured by flow cytometry; tumor-cytotoxic effects of cytotoxic T lymphocytes (CTLs) were measured by the MTT assay. Active immunotherapy was applied to SD osteosarcoma model rats via subcutaneous injection of the tumor vaccine. Significant potentiation of T lymphocyte proliferation was observed in both groups. In the homograft group, the CD8+/CD4+ ratio was elevated to 78.2 from 55.1% after stimulation (P < 0.05) whereas the CD4+ cell percentage was reduced from 61.3 to 21.2% (P < 0.05). Similarly, in the allograft group the CD8+ and CD4+ cell percentages significantly increased (33.8 to 69.6%) or decreased (61.3 to 28.1%) X. Fang et al. 11764©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 11763-11770 (2015) after stimulation, respectively (P < 0.05). The preferential homograft group response was not significant (P > 0.05). Induced UMR106-specific CTLs showed a significantly higher tumor-cytotoxic effect after stimulation (P < 0.05). After DOF active immunotherapy, tumor bodies displayed atrophy or disappearance, leading to higher survival times and rates (60 and 70% in the allograft and homograft groups) (P < 0.05). This study demonstrated that osteosarcoma immunotherapy using a DC-fused tumor vaccine can effectively stimulate T lymphocyte proliferation and induce the tumor-cytotoxic activity of CTLs.

show abstract

“…However, we still need to enroll patients affected by other cancer types to validate the applicability of this protocol to other cancer types. By using a mathematical approach, one study suggested that calculation of CD8+ or CD4+ T-cell percentages on early days could predict the CIK expansion quality [57]. Other strategies were used to improve the expansion and function of CIK cells, such as the addition or replacement of cytokines, like IL-7, IL-15 or thymoglobulin, instead of IL-2 [58][59][60][61], addition of allogeneic APCs, depletion of regulatory T cells, or pharmacological interventions [15,62].…”

Section: Plos Onementioning

confidence: 99%

Immunophenotype and antitumor activity of cytokine-induced killer cells from patients with hepatocellular carcinoma

Yang

Huang

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Background Cytokine-induced killer (CIK) cells are heterogeneous lymphocytes from human peripheral blood mononucleated cells (PBMCs) co-cultured with several cytokines. The main purpose of this study is to evaluate the functional characteristics and anticancer ability of CIK cells from hepatocarcinoma (HCC) patients. Methods CIK cells were activated ex-vivo and expanded from PBMCs from HCC patients. The immunophenotype and the ex-vivo killing ability of CIK cells were evaluated. Human CIK cells were intravenously injected into NOD/SCID mice to evaluate the in vivo anticancer ability. Results More than 70% of CIK cells were CD3+CD8+, and 15%–30% were CD3+CD56+. These cells expressed an increased number of activated natural killer (NK) receptors, such as DNAM1 and NKG2D, and expressed low-immune checkpoint molecules, including PD-1, CTLA-4, and LAG-3. Among the chemokine receptors expressed by CIKs, CXCR3 and CD62L were elevated in CD8+ T cells, representing the trafficking ability to inflamed tumor sites. CIK cells possess the ex-vivo anticancer activity to different cell lines. To demonstrate in vivo antitumor ability, human CIK cells could significantly suppress the tumor of J7 bearing NOD/SCID mice. Furthermore, human immune cells could be detected in the peripheral blood and on the tumors after CIK injection. Conclusions This study revealed that CIK cells from HCC patients possess cytotoxic properties, and express increased levels of effector NK receptors and chemokine molecules and lower levels of suppressive checkpoint receptors. CIK cells can suppress human HCC ex-vivo and in vivo. Future clinical trials of human CIK cell therapy for HCC are warranted.

show abstract

Multivariate statistical data analysis as a tool to analyze ex vivo expansion dynamics of cytokine-induced killer cells

Abstract: Background: Cytokine-induced killer (CIK) cells, obtained after mononucleated cell stimulation with interferon-g, interleukin-2, and anti-CD3 antibody, are constituted by CD3

Cited by 7 publications

References 17 publications

Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood

Phenotypic and functional characterization of cytokine-induced killer cells derived from preterm and term infant cord blood

Effectiveness evaluation of dendritic cell immunotherapy for osteosarcoma on survival rate and in vitro immune response

Immunophenotype and antitumor activity of cytokine-induced killer cells from patients with hepatocellular carcinoma

Contact Info

Product

Resources

About