Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition

Liu, Dongfang; Xu, Lu; Yang, Fan; Li, Dongdong; Gong, Feili; Xu, Tao

doi:10.1073/pnas.0405737102

Cited by 37 publications

(36 citation statements)

References 31 publications

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“…Capacitance of membrane was measured with the method described by Liu et al [3]. Briefly, conventional whole-cell patch-clamp measurements were performed by using an EPC-9 patch-clamp amplifier and PULSE software (HEKA, Lambrecht, Germany).…”

Section: Membrane Capacitance Measurementmentioning

confidence: 99%

“…-triggered post-exocytosis, endocytosis. The cytotoxicity and exocytosis of NK cells is usually triggered by target cell, for example, virus-infected cells, tumor cells, or heterologous cells [1,3,20]. In order to confirm whether the endocytosis triggered by target cell occurs, FM1-43FX, well-known to researchers in membrane dynamics [21,22] as an inducer of fluorescent emissions, in double-molecular layers (not in single), was used to label and show the endocytosis on the surface membrane of the cell.…”

Section: Endocytosis Occurred In Nk92 Cells Stimulated By Target Cellsmentioning

confidence: 99%

“…They are critical in the defense against viral infections and tumors [1], exerting their cytotoxicity through the exocytosis of cytotoxic granules, which serves both as the secretory granule and as the lysosome called secretory lysosome [2][3][4]. When a cytotoxic lymphocyte recognizes a target cell, cytotoxic granules move to the immune synapse where the cytotoxic granules fuse with the plasma membrane and release effector molecules into the synaptic cleft [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

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Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

Zheng²,

Yang

et al. 2010

Cell. Mol. Life Sci.

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When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft) are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation of immune cells.

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Section: Membrane Capacitance Measurementmentioning

confidence: 99%

Section: Endocytosis Occurred In Nk92 Cells Stimulated By Target Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

Zheng²,

Yang

et al. 2010

Cell. Mol. Life Sci.

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“…Induction of cytotoxicity is possible in NK cells within minutes, in contrast with the slower conventional induction of the T-cell immune response (9). Approximately 5% to 15% of human blood lymphocytes are NK cells (CD56 þ , CD3/14/19 À ), 90% of which are CD56dim, with most of them being CD16 þ , and they are responsible for early innate immunity and antibodydependent cell-mediated cytotoxicity (ADCC) against infection or cancer through IFNg, perforin, granzyme, FasL, or TRAIL (10).…”

Section: Nk Cell Biologymentioning

confidence: 99%

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Leung

2014

Clinical Cancer Research

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Natural killer (NK) cells are normal white blood cells capable of killing malignant cells without prior sensitization. Allogeneic NK cell infusions are attractive for cancer therapy because of non-cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, failure of homing to tumor sites, effector dysfunction, exhaustion, and tumor cell evasion. Capitalizing on the wealth of knowledge generated by recent NK cell biology studies and the advancements in biotechnology, substantial progress has been made recently in improving therapeutic efficiency and reducing side effects. A multipronged strategy is essential, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of adult and pediatric cancers are under way. The unique properties of human NK cells open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies. Clin Cancer Res; 20(13); 3390-400. Ó2014 AACR.

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“…As granule convergence to the MTOC is an early step in the preparation of an NK cell for cytotoxicity 32,33 this is an unexpected finding; however, movement and exocytosis of secretory lysosomes in NK cells can occur independently from MTOC polarization. 32,[34][35][36] As direct visualization of conjugate formation clearly documents an extension and flattening of TIML-NK cell shape toward the immunological synapse (IS) (Fig. 5B, white arrowheads) and formation of multiple F-actin-rich cytoplasmic projections (Fig.…”

Section: Timl-nk Cells Display Enhanced Perforin Synthesismentioning

confidence: 99%

Tumor-priming converts NK cells to memory-like NK cells

et al. 2017

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Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs.-leukemia (GvL) reactivity. Here, we provide substantial evidence that priming of naive human NK cells with pediatric acute B cell leukemia or acute myeloid leukemia specimens induces a functional conversion to tumor-induced memory-like (TIML)-NK cells displaying a heightened tumorspecific cytotoxicity and enhanced perforin synthesis. Cell cycles analyses reveal that tumor-priming sustainably alters the balance between NK cell activation and apoptosis in favor of survival. In addition, gene expression patterns differ between TIML-and cytokine-induced memory-like (CIML)-NK cells with the magnitude of regulated genes being distinctly higher in TIML-NK cells. As such, the tumor-induced conversion of NK cells triggers the emergence of a so far unacknowledged NK cell differentiation stage that might promote GvL effects in the context of adoptive cell transfer.

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Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition

Cited by 37 publications

References 31 publications

Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

Infusions of Allogeneic Natural Killer Cells as Cancer Therapy

Tumor-priming converts NK cells to memory-like NK cells

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