Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

Chen, Jionghuang; Xiang, Jianyang; Ding, Guoping; Cao, Liping

doi:10.1631/jzus.b1500266

Cited by 29 publications

(21 citation statements)

References 29 publications

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“…Since CD3 + T lymphocytes are the main components of CIK cells and perforin is important in the antitumor effects of CIK cells (17), an immunohistochemical study was further performed on the excised tumor tissue with anti-CD3 and anti-perforin antibodies. The results revealed that there was significantly more accumulation of CD3 + T lymphocytes and perforin in tumor tissue treated with CIK cells plus NaHCO 3 compared with tumor tissue treated with CIK cells alone (Fig.…”

Section: Resultsmentioning

confidence: 99%

NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells

et al. 2016

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The extracellular pH is lower inside solid tumors than in normal tissue. The acidic environment inhibits the cytotoxicity of lymphocytes in vitro and promotes tumor cell invasion. In the present study, both in vitro and in vivo experiments were conducted to investigate how NaHCO3 would affect the antitumor activities of cytokine-induced killer (CIK) cells against hepatocellular carcinoma (HCC) cells. For the in vitro experiments, HepG2 cells were cultured at pH 6.5 and 7.4 in the presence of CIK cells or CIK cell-conditioned medium (CMCIK). For the in vivo experiments, nude mice were xenografted with HepG2-luc cells and divided into four groups: i) CIK cells injection plus NaHCO3 feeding; ii) CIK cells injection plus drinking water feeding; iii) normal saline injection plus NaHCO3 feeding; and iv) normal saline injection plus drinking water feeding. The results indicated that the viability and growth rate of HepG2 cells were remarkably suppressed when co-cultured with CIK cells or CMCIK at pH 7.4 compared with those of HepG2 cells cultured under the same conditions but at pH 6.5. In the xenograft study, a marked synergistic antitumor effect of the combined therapy was observed. NaHCO3 feeding augmented the infiltration of cluster of differentiation 3-positive T lymphocytes into the tumor mass. Taken together, these data strongly suggest that the antitumor activities of CIK cells against HepG2 cells were negatively affected by the acidic environment inside the tumors, and neutralizing the pH (for example, via NaHCO3 administration), could therefore reduce or eliminate this influence. In addition, it should be recommended that oncologists routinely prescribe soda water to their patients, particularly during CIK cell therapy.

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Section: Resultsmentioning

confidence: 99%

NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells

et al. 2016

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“…A study of co-culture system between CAFs and iCCA cells demonstrated that miR-195, carried by CAF-derived exosomes, could inhibit tumor proliferation and invasion in vitro [101]. Another study conducted by Chen et al demonstrated that CCA-derived exosomes support iCCA cells to escape the attack of the immune system by preventing cytokine-induced killer (CIK) cells from producing molecules with anticancer effect, such as tumor necrosis factor (TNF)-α and perforin [102]. Hence, the in vitro study of exosomes-TME interactions may be important for the development of new therapeutic approaches.…”

Section: D Models: Cell Lines and Primary Cell Culturesmentioning

confidence: 99%

Evolution of the Experimental Models of Cholangiocarcinoma

Massa

Varamo

Vita

et al. 2020

Cancers

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Cholangiocarcinoma (CCA) is a rare, aggressive disease with poor overall survival. In advanced cases, surgery is often not possible or fails; in addition, there is a lack of effective and specific therapies. Multidisciplinary approaches and advanced technologies have improved the knowledge of CCA molecular pathogenesis, highlighting its extreme heterogeneity and high frequency of genetic and molecular aberrations. Effective preclinical models, therefore, should be based on a comparable level of complexity. In the past years, there has been a consistent increase in the number of available CCA models. The exploitation of even more complex CCA models is rising. Examples are the use of CRISPR/Cas9 or stabilized organoids for in vitro studies, as well as patient-derived xenografts or transgenic mouse models for in vivo applications. Here, we examine the available preclinical CCA models exploited to investigate: (i) carcinogenesis processes from initiation to progression; and (ii) tools for personalized therapy and innovative therapeutic approaches, including chemotherapy and immune/targeted therapies. For each model, we describe the potential applications, highlighting both its advantages and limits.

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“…The proteomics analysis of normal bile duct cells and CCA cells confirmed the differences between these two cell types, and these differences need to be further studied. Moreover, exosomes from another CCA cell line (RBE) could inhibit the antitumor activity of cytokine-induced killer (CIK) cells by downregulating the populations of CD3 + , CD8 + , Circ-0000284 HuCCT1 and RBE Gene LY6E Enhancing the migration, invasion and proliferation of CCA cells [86] NK (CD56 + ) and CD3 + CD56 + cells and secreting TNF-α and perforin [65]. According to some research, mutations in the IDH1 gene is common in a variety of tumors, including iCCA [66,67].…”

Section: The Function Of Evs In Tumor Microenvironmentmentioning

confidence: 99%

The role of extracellular vesicles in cholangiocarcinoma

Bai

et al. 2020

Cancer Cell Int

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Cholangiocarcinoma (CCA) is a rare tumor that arises from cholangiocytes, the epithelial cells of the bile duct. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis and high recurrence rate. Due to the lack of specific biomarkers, it is difficult to diagnose CCA early and evaluate prognosis. Extracellular vesicles (EVs), which include apoptotic bodies, microvesicles and exosomes, have emerged as having important roles in cellto-cell communication in both normal physiology and pathological conditions. Some research has found that EVs play a crucial role in the occurrence and development of CCA. EVs can carry specific molecular substances such as nucleic acids and proteins, which have potential for the diagnosis and therapy of CCA. This article reviews the current knowledge on the role of EVs in CCA. We highlight EVs and their functions in the physiology and pathophysiology of CCA, and discuss their therapeutic potential and their role as biomarkers.

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Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin

Cited by 29 publications

References 29 publications

NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells

NaHCO3 enhances the antitumor activities of cytokine-induced killer cells against hepatocellular carcinoma HepG2 cells

Evolution of the Experimental Models of Cholangiocarcinoma

The role of extracellular vesicles in cholangiocarcinoma

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