The breast tumor microenvironment alters the phenotype and function of natural killer cells

Krneta, Tamara; Gillgrass, Amy; Chew, Marianne V.; Ashkar, Ali A.

doi:10.1038/cmi.2015.42

Cited by 71 publications

(55 citation statements)

References 38 publications

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“…Indeed, in our study, NK cell deficiency completely abolished the IL‐33‐mediated inhibition of tumor development in 4T1‐bearing mice, but not B16‐F10‐bearing mice. Besides, the heterogeneity of the TME also affects the antitumor immune response . Metastatic tumors are more sensitive to NK cells than CD8 + T cells, in contrast to primary tumors, in line with our observations in the 4T1 metastasis model.…”

Section: Discussionsupporting

confidence: 88%

Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development

Zhang

Miao

et al. 2019

Intl Journal of Cancer

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Increasing evidence suggests that IL‐33 plays an important role in regulating tumor development. However, conflicting results, obtained from numerous studies, have highlighted the divergent functions of IL‐33. The detailed mechanisms by which IL‐33 modulates tumor development merit further investigation. Here, we report that IL‐33 administration can effectively inhibit the development of pulmonary metastasis of breast cancer in a mouse. In our model, IL‐33 promotes the production of TNF‐α by macrophages, which increases IL‐33 specific receptor (ST2) expression on natural killer (NK) cells and is pivotal in IL‐33‐induced NK cell activation. IL‐33 treatment also facilitates the production of CCL5 in the lung by eosinophils and CD8+ T cells, which mediates the recruitment of NK cells to the tumor microenvironment. The systemic activation and local recruitment of NK cells result in potent tumor rejection in the lung. Our study reports a novel mechanism for the IL‐33‐meditated suppression of metastatic cancer and provides potential therapeutic strategies for targeting metastatic tumor.

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Section: Discussionsupporting

confidence: 88%

Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development

Zhang

Miao

et al. 2019

Intl Journal of Cancer

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“…In NK cells, the greater the alloreactivity between donor and recipient is, the better the antitumor efficacy is [13][14][15][16]. This relationship is consistent with the mechanisms of NK-cell recognition, whereby autologous NK cells are potentially inhibited by self MHC class-I molecules on cancer cells.…”

Section: Adoptive Cell Transfer (Act)supporting

confidence: 63%

Challenges of NK cell-based immunotherapy in the new era

2018

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Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.

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“…For example, high infiltration of TAM in the tumours correlates with low number of interferon‐ γ ‐expressing active NK cells in human hepatocellular carcinoma and TAM from the tumour reduce activation and survival of NK cells . It is also reported that TAM isolated from the PyMT mouse mammary tumours significantly reduces cytotoxicity of NK cells in vitro . These results suggest that TAM depletion by blocking TAM recruitment or survival signals (e.g.…”

Section: Tam Targeting For Adoptive Ctl Transfer Therapymentioning

confidence: 91%

Macrophage targeting: opening new possibilities for cancer immunotherapy

2018

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SummaryTumour‐infiltrating immune cells regulate tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour‐killing ability of CTL, the augmentation of CTL‐induced antitumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant antitumour effects in patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, these therapies are not efficient in a certain fraction of patients and tumour types with tumour cell‐intrinsic mechanisms such as impaired antigen presentation and/or tumour cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve the efficacy of immunotherapies as these cells can suppress the functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.

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The breast tumor microenvironment alters the phenotype and function of natural killer cells

Cited by 71 publications

References 38 publications

Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development

Interleukin‐33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development

Challenges of NK cell-based immunotherapy in the new era

Macrophage targeting: opening new possibilities for cancer immunotherapy

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