Natural killer cell-mediated immunosurveillance of human cancer

Malmberg, Karl‐Johan; Carlsten, Mattias; Björklund, Andreas; Sohlberg, Ebba; Bryceson, Yenan T.; Ljunggren, Hans‐Gustaf

doi:10.1016/j.smim.2017.08.002

Cited by 240 publications

(202 citation statements)

References 148 publications

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“…NK cells are innate lymphocytes that can control cancer by interacting with tumor cells and/or regulating anticancer immunity in the tumor microenvironment (TME). NK cells display potent cytotoxicity activity against tumor cells that express low levels of MHC class I molecules and/or increased levels of tumor or stress associated activating ligands …”

Section: Introductionmentioning

confidence: 99%

“…NK cells display potent cytotoxicity activity against tumor cells that express low levels of MHC class I molecules and/or increased levels of tumor or stress associated activating ligands. [10][11][12] Despite these immune responses, in many cancers, a proportion of cells are able to escape the immune system by a mechanism called "immune evasion". 13 It is believed that "immune checkpoints" can play an important role in this escape mechanism.…”

Section: Introductionmentioning

confidence: 99%

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NK‐ and T‐cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti‐CTLA‐4 therapy

Sottile

Tannazi

Johansson

et al. 2019

Intl Journal of Cancer

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Malignant mesothelioma (MM) is a highly aggressive form of cancer with limited treatment options. Although the role of NK cells has been studied in many solid tumors, the pattern of NK‐cell subsets and their recognition of mesothelioma cells remain to be explored. We used RNA expression data of MM biopsies derived from the cancer genome atlas to evaluate the immune cell infiltrates. We characterized the phenotype of circulating NK and T cells of 27 MM patients before and after treatment with an anti‐CTLA‐4 antibody (tremelimumab). These immune cell profiles were compared to healthy controls. The RNA expression data of the MM biopsies indicated the presence of NK cells in a subgroup of patients. We demonstrated that NK cells recognize MM cell lines and that IL‐15 stimulation improved NK cell‐mediated lysis in vitro. Using multivariate projection models, we found that MM patients had a perturbed ratio of CD56bright and CD56dim NK subsets and increased serum concentrations of the cytokines IL‐10, IL‐8 and TNF‐α. After tremelimumab treatment, the ratio between the CD56bright and CD56dim subsets shifted back towards physiological levels. Furthermore, the improved overall survival was correlated with low TIM‐3+CD8+ T‐cell frequency, high DNAM‐1+CD56dim NK‐cell frequency and high expression levels of NKp46 on the CD56dim NK cells before and after immune checkpoint blockade. Together, our observations suggest that NK cells infiltrate MM and that they can recognize and kill mesothelioma cells. The disease is associated with distinct lymphocytes patterns, some of which correlate with prognosis or are affected by treatment with tremelimumab.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NK‐ and T‐cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti‐CTLA‐4 therapy

Sottile

Tannazi

Johansson

et al. 2019

Intl Journal of Cancer

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“…Immune surveillance of tumors is an important host protection process to inhibit carcinogenesis 35,36 and NK cells are one of the key immune cells for immune surveillance of tumors. 37,38 Some experimental and clinical studies demonstrated that adaptive transfer of IL-2-stimulated NK cells from normal (donor) liver perfusate could prevent HCC recurrence. 39,40 Based on the target mRNA search, we selected CD69, which plays a crucial role in NK cell activity, 23 as a potential target mRNA for miR-92b.…”

Section: Discussionmentioning

confidence: 99%

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence

Nakano

Chen

Wang

et al. 2019

American Journal of Transplantation

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A recurrence of hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) is one of the major concerns reflecting the higher mortality of HCC. This study aimed to explore the impact of circulating exosomes on HCC development and recurrence. One-shot transfusion of hepatoma serum to naïve rats induced liver cancer development with gradual elevation of alpha-fetoprotein (AFP), but exosome-free hepatoma serum failed to induce AFP elevation. The microarray analysis revealed miR-92b as one of the highly expressing microribonucleic acids in hepatoma serum exosomes. Overexpression of miR-92b enhanced the migration ability of liver cancer cell lines with active release of exosomal miR-92b. The hepatoma-derived exosomal miR-92b transferred to natural killer (NK) cells, resulting in the downregulation of CD69 and NK cell-mediated cytotoxicity. Furthermore, higher expression of miR-92b in serum exosomes was confirmed in HCC patients before LDLT, and its value at 1 month after LDLT was maintained at a higher level in the patients with posttransplant HCC recurrence. In summary, we demonstrated the impact of circulating exosomes on liver cancer development, partly through the suppression of CD69 on NK cells by hepatoma-derived exosomal miR-92b. The value of circulating exosomal miR-92b may predict the risk of posttransplant HCC recurrence. K E Y W O R D Sbasic (laboratory) research/science, biomarker, cancer/malignancy/neoplasia: risk factors, cellular biology, immunobiology, liver transplantation/hepatology, microarray/gene array, molecular biology: micro RNA, natural killer (NK) cells/NK receptors, translational research/ science 1 | INTRODUC TI ON Hepatocellular carcinoma (HCC) is the second leading cause of death from cancer in the world. 1 In general, malignant tumor regions are treated by radiofrequency ablation (RFA) or transarterial embolization (TAE) and/or removed by surgical resection.Our group compared the disease-free survival of HCC patients between surgical resection and RFA in the Barcelona Clinic Liver

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“…NK cell activation depends on a delicate balance between activating and inhibitory signals and the integration of these pathways may prevent NK self‐reactivity and governs NK cell activation in the presence of cells in “distress” . NK cells, once activated, can be actively cytotoxic through the release of perforin and granzymes and can secrete cytokines, such as IFNγ, thus participating in the shaping of the adaptive immune responses . NK cell effector functions also include antibody‐dependent cell cytotoxicity (ADCC): NK cells recognize antibody‐coated target cells through the FcγRIIIA (CD16), which is coupled to CD3ζ and FcRγ transducing chains bearing the ITAM (immunoreceptor tyrosine‐based activation motif) domains .…”

Section: Introductionmentioning

confidence: 99%

“…3,4 NK cells, once activated, can be actively cytotoxic through the release of perforin and granzymes and can secrete cytokines, such as IFNγ, thus participating in the shaping of the adaptive immune responses. [4][5][6][7][8] NK cell effector functions also include antibody-dependent cell cytotoxicity (ADCC): NK cells recognize antibody-coated target cells through the FcγRIIIA (CD16), which is coupled to CD3ζ and FcRγ transducing chains bearing the ITAM (immunoreceptor tyrosine-based activation motif) domains. 3,9 NK cells recognize damaged, stressed, infected or tumour cells, which upregulate or express de novo ligands interacting with activating NK cell receptors.…”

Section: Introductionmentioning

confidence: 99%

The yin‐yang of the interaction between myelomonocytic cells and NK cells

et al. 2018

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NK cells are innate lymphoid cells, which play a key role in the immune response to cancer and pathogens and participate in the shaping of adaptive immunity. NK cells engage in a complex bidirectional interaction with myelomonocytic cells. In particular, macrophages, dendritic cells and neutrophils promote differentiation and effector function of NK cells and, on the other hand, myelomonocytic cells express triggers of checkpoint blockade (eg PD-L1) and other immunosuppressive molecules, which negatively regulate NK cell function. In addition, NK cells express high levels of IL-1R8, which acts as a checkpoint for IL-18 driven differentiation and activation of NK cells. Evidence suggests that targeting the myeloid cell-NK cell crosstalk unleashes effective anti-tumour and anti-viral resistance.

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Natural killer cell-mediated immunosurveillance of human cancer

Cited by 240 publications

References 148 publications

NK‐ and T‐cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti‐CTLA‐4 therapy

NK‐ and T‐cell subsets in malignant mesothelioma patients: Baseline pattern and changes in the context of anti‐CTLA‐4 therapy

Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence

The yin‐yang of the interaction between myelomonocytic cells and NK cells

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