Cytokine-induced killer (CIK) cells are an expanded heterogeneous cell population with an enriched NK-T phenotype (CD3+CD56+). Due to the convenient and relatively inexpensive expansion capability, together with low incidence of graft host disease (GVHD) in allogeneic cancer patients, CIK cells are a promising candidate for immunotherapy. It is well known that natural killer group 2D (NKG2D) plays an important role in CIK cell-mediated antitumor activity; however, it remains unclear whether its engagement alone is sufficient or if it requires additional co-stimulatory signals to activate the CIK cells. Likewise, the role of 2B4 has not yet been identified in CIK cells. Herein, we investigated the individual and cumulative contribution of NKG2D and 2B4 in the activation of CIK cells. Our analysis suggests that (a) NKG2D (not 2B4) is implicated in CIK cell (especially CD3+CD56+ subset)-mediated cytotoxicity, IFN-γ secretion, E/T conjugate formation, and degranulation; (b) NKG2D alone is adequate enough to induce degranulation, IFN-γ secretion, and LFA-1 activation in CIK cells, while 2B4 only provides limited synergy with NKG2D (e.g., in LFA-1 activation); and (c) NKG2D was unable to costimulate CD3. Collectively, we conclude that NKG2D engagement alone suffices to activate CIK cells, thereby strengthening the idea that targeting the NKG2D axis is a promising approach to improve CIK cell therapy for cancer patients. Furthermore, CIK cells exhibit similarities to classical invariant natural killer (iNKT) cells with deficiencies in 2B4 stimulation and in the costimulation of CD3 with NKG2D. In addition, based on the current data, the divergence in receptor function between CIK cells and NK (or T) cells can be assumed, pointing to the possibility that molecular modifications (e.g., using chimeric antigen receptor technology) on CIK cells may need to be customized and optimized to maximize their functional potential.
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http://dx.doi.org/10.3389/fimmu.2021.731767 | DOI Listing |
J Transl Med
December 2024
Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Background: Immunotherapy utilizing dendritic cells (DCs) and cytokine-induced killer (CIK) cells is a promising treatment approach for solid tumors. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DC-CIK immunotherapy by assessing overall survival, progression-free survival, overall response rate, disease control rate, and adverse events in relevant randomized controlled trials. The results of this analysis will contribute to optimizing treatment strategies and improving cancer immunotherapy outcomes.
View Article and Find Full Text PDFBMC Immunol
December 2024
Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Purpose: Immunotherapy is a promising treatment for cancers but should be optimized for malignant gliomas. Because of immune privilege feature of the brain, local administration of immunotherapy may be a promising strategy for malignant glioma treatment. Identification of patients who may benefit from local immunotherapy is essential.
View Article and Find Full Text PDFMol Biol Rep
December 2024
Yunnan Key Laboratory of Laboratory Medicine, Yunnan Province Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.
Background: Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear.
View Article and Find Full Text PDFExp Oncol
December 2024
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine.
Aim: To investigate the effect of bacteria of the genus Bifidobacterium and the extracellular metabolite of B. subtilis IMV B-7724 on the antitumor immune response of mice with a model tumor.
Materials And Methods: The study was conducted on Balb/c mice with transplanted solid Ehrlich adenocarcinoma (ACE).
Cell Mol Life Sci
December 2024
Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, 66421, Homburg, Germany.
Flower, a highly conserved protein, crucial for endocytosis and cellular fitness, has been implicated in cytotoxic T lymphocyte (CTL) killing efficiency through its role in cytotoxic granule (CG) endocytosis at the immune synapse (IS). This study explores the molecular cues that govern Flower-mediated CG endocytosis by analyzing uptake of Synaptobrevin2, a protein specific to CG in mouse CTL. Using immunogold electron microscopy and total internal fluorescence microscopy, we found that Flower translocates in a stimulus-dependent manner from small vesicles to the IS, thereby ensuring specificity in CG membrane protein recycling.
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