Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

Ducimetière, Laura; Lucchiari, Giulia; Litscher, Gioana; Nater, Marc; Heeb, Laura; Núñez, Nicolás Gonzalo; Wyss, Laura; Burri, Dominik; Vermeer, Marijne; Gschwend, Julia; Moor, Andreas E.; Becher, Burkhard; Broek, Maries van den; Tugues, Sònia

doi:10.1073/pnas.2026271118

Cited by 76 publications

(78 citation statements)

References 55 publications

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“…In the current study, NK cells have been found to be compromised in several cancer types, and skewed NK cells contributes to cancer progression via tumor escape and immunosuppression. Downregulation of activating receptor expression on NK cells and impaired NK function are common mechanisms of immune evasion in cancer, and have been associated with tumor progression [28]. Competitive interactions between TIGIT (T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif [ITIM] domains) and CD226 receptors with cognate ligands, such as nectins and poliovirus receptor (PVR), play a critical role in TIGIT-driven immune suppression, and anti-TIGIT therapy is designed to reverse this suppression by inhibiting TIGIT-PVR binding [29].…”

Section: Discussionmentioning

confidence: 99%

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Chang

Tsai

Hung

et al. 2021

Cancers

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Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.

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Section: Discussionmentioning

confidence: 99%

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Chang

Tsai

Hung

et al. 2021

Cancers

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“…'Immune Profiling in Multiple Myeloma' (NCT04135079) does not state in its aims that it will be looking at ILCs specifically. The impact of targeting ILCs should not be underestimated and is only beginning to come into view [146]. Unravelling the immunology of ILCs in MM is likely to provide better options for the treatment of MM and other malignancies.…”

Section: Clinical Trialsmentioning

confidence: 99%

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

Szudy‐Szczyrek

Ahern

Kozioł

et al. 2021

Cancers

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Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to environmental stimuli, ILCs change their phenotype and functions, and influence the activity of other cells in the microenvironment. ILC dysfunction can lead to a wide variety of diseases, including cancer. ILC can be divided into three subgroups: ILC Group 1, comprising NK cells and ILC1; Group 2, including ILC2 alone; and Group 3, containing Lymphoid Tissue inducers (LTi) and ILC3 cells. While Group 1 ILCs mainly exert antitumour activity, Group 2 and Group 3 ILCs are protumorigenic in nature. A growing body of preclinical and clinical data support the role of ILCs in the pathogenesis of multiple myeloma (MM). Therefore, targeting ILCs may be of clinical benefit. In this manuscript, we review the available data on the role of ILCs in MM immunology and therapy.

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“…Thus, so far, there are no specific mouse models to precisely investigate the role of liver ILC1 in HCC development and progression. Recent investigations using preclinical models of liver metastasis suggest that ILC1 are essential to control metastatic seeding, whereas NK cells restrain tumor outgrowth [302].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

Jacquelot

Seillet

Souza-Fonseca-Guimarães

et al. 2021

IJMS

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Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1) are specific innate lymphoid cell subsets that are key for the detection and elimination of pathogens and cancer cells. In liver, while they share a number of characteristics, they differ in many features. These include their developmental pathways, tissue distribution, phenotype and functions. NK cells and ILC1 contribute to organ homeostasis through the production of key cytokines and chemokines and the elimination of potential harmful bacteria and viruses. In addition, they are equipped with a wide range of receptors, allowing them to detect “stressed cells’ such as cancer cells. Our understanding of the role of innate lymphoid cells in hepatocellular carcinoma (HCC) is growing owing to the development of mouse models, the progress in immunotherapeutic treatment and the recent use of scRNA sequencing analyses. In this review, we summarize the current understanding of NK cells and ILC1 in hepatocellular carcinoma and discuss future strategies to take advantage of these innate immune cells in anti-tumor immunity. Immunotherapies hold great promise in HCC, and a better understanding of the role and function of NK cells and ILC1 in liver cancer could pave the way for new NK cell and/or ILC1-targeted treatment.

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Conventional NK cells and tissue-resident ILC1s join forces to control liver metastasis

Cited by 76 publications

References 55 publications

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

Natural Killer Cells and Type 1 Innate Lymphoid Cells in Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

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