Identification of a protein associated with the activity of cytokine-induced killer cells

Jingsong Cao1,2, Cong Chen3, Yongqiang Gao1,2

  • 1Institute of Pathogenic Biology, Medical College, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang, Hunan 421001, P.R. China.

Oncology Letters
|November 23, 2017
PubMed

Insights

Gentamicin treatment reduces the antitumor ability of cytokine-induced killer cells (CIKs). This study identifies haptoglobin as a key protein downregulated by gentamicin, impacting CIK activity and offering insights into immunotherapy enhancement.

Area of Science:

  • Immunology
  • Cancer Research
  • Biochemistry

Background:

  • Cytokine-induced killer cells (CIKs) are utilized in adoptive immunotherapy for their antitumor capabilities.
  • The specific molecular mechanisms regulating CIK activity, particularly in the context of hepatoma, require further elucidation.

Purpose of the Study:

  • To investigate the impact of gentamicin on CIK cytotoxicity against hepatoma.
  • To identify proteins differentially expressed in CIKs following gentamicin treatment and assess their association with CIK activity.

Main Methods:

  • One-dimensional gel electrophoresis and liquid chromatography-mass spectrometry were employed to identify differentially expressed proteins.
  • Western blotting was used to validate the expression levels of the identified protein (haptoglobin).
  • Quantitative analysis of haptoglobin mRNA expression was performed.

Main Results:

  • Gentamicin treatment significantly downregulated CIK cytotoxicity against hepatoma by 1.61-fold.
  • A protein, designated P43, was identified as human haptoglobin and was significantly downregulated by 1.22-fold.
  • Haptoglobin protein and mRNA expression were significantly reduced following gentamicin treatment, correlating with decreased CIK activity.

Conclusions:

  • Haptoglobin expression is associated with the antitumor activity of CIKs.
  • The downregulation of haptoglobin by gentamicin may contribute to the observed decrease in CIK efficacy.
  • These findings provide a basis for further research into CIK activity enhancement mechanisms.

Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
9.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.2K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
7.6K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
16.4K
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
8.9K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
2.7K