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

2021 ◽  
Vol 22 (16) ◽  
pp. 9044
Author(s):  
Nicolas Jacquelot ◽  
Cyril Seillet ◽  
Fernando Souza-Fonseca-Guimaraes ◽  
Adrian G. Sacher ◽  
Gabrielle T. Belz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nk Cells ◽  
Cancer Cells ◽  
Natural Killer ◽  
Current Knowledge ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Great Promise ◽  
Wide Range

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.

Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells

2017 ◽  
Vol 18 (9) ◽  
pp. 1004-1015 ◽  
Author(s):  
Yulong Gao ◽  
Fernando Souza-Fonseca-Guimaraes ◽  
Tobias Bald ◽  
Susanna S Ng ◽  
Arabella Young ◽  
...  
Keyword(s):  
Nk Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

scholarly journals Toxoplasma gondiiInfection Drives Conversion of NK Cells into ILC1s

2019 ◽  
Author(s):  
Eugene Park ◽  
Swapneel J. Patel ◽  
Qiuling Wang ◽  
Prabhakar S. Andhey ◽  
Konstantin Zaitsev ◽  
...  
Keyword(s):  
Steady State ◽  
Tumor Microenvironment ◽  
Toxoplasma Gondii ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Conversion ◽  
Ongoing Infection

AbstractInnate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here we describeToxoplasma gondiiinfection converts NK cells into cells resembling steady-state ILC1s that are heterogeneous and distinct from both steady-state NK cells and ILC1s in uninfected mice. Most toxoplasma-induced ILC1s were Eomes-dependent, indicating that NK cells can give rise to Eomes−Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

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

2020 ◽  
Author(s):  
Laura Ducimetière ◽  
Giulia Lucchiari ◽  
Gioana Litscher ◽  
Marc Nater ◽  
Laura Heeb ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Nk Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Great Promise ◽  
Type I ◽  
Metastatic Niche

SUMMARYThe liver is a major metastatic target organ, and little is known about the role of immunity in controlling hepatic metastases. Here, we discovered that the concerted and non-redundant action of two innate lymphocyte subpopulations, conventional NK cells (cNKs) and tissue-resident type I Innate Lymphoid Cells (trILC1s), is essential for anti-metastatic defense. Using different preclinical models for liver metastasis, we found that trILC1 control metastatic seeding, whereas cNKs restrain outgrowth. The antimetastatic activity of cNKs is regulated in a tumor type-specific fashion. Thereby, individual cancer cell lines orchestrate the emergence of cNK subsets with unique phenotypic and functional traits. Understanding cancer-cell- as well as innate-cell-intrinsic factors will allow the exploitation of hepatic innate cells for development of novel cancer therapies.SignificanceInnate lymphoid cells hold great promise for the treatment of metastases. Development of effective therapies based on these versatile immune cells, however, is hampered by our limited knowledge of their behavior in the metastatic niche. Here, we describe that defense against liver metastasis requires the collaboration between two innate lymphocyte subsets, conventional NK cells (cNKs) and tissue-resident type I innate lymphoid cells (trILC1s). We show that different cancers generate their own particular metastatic niche inducing specific changes in cNKs and trILC1s. Further, we uncover specific cNK subsets that can be manipulated to improve their anti-metastatic potential. Our work contributes to understanding how cancer-specific factors and hepatic innate lymphocytes exert mutual influence and how this can be exploited for therapeutic purposes.HighlightscNKs and trILC1s collaborate to control hepatic metastasistrILC1s restrict seeding and cNKs control outgrowth of cancer cells in the liverIndividual cancer cell lines orchestrate a distinct metastatic nicheThe metastatic niche dictates the phenotype and function of cNKs

scholarly journals NK cells and type 1 innate lymphoid cells: partners in host defense

2016 ◽  
Vol 17 (7) ◽  
pp. 758-764 ◽  
Author(s):  
Hergen Spits ◽  
Jochem H Bernink ◽  
Lewis Lanier
Keyword(s):  
Nk Cells ◽  
Host Defense ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

scholarly journals Sialyl SSEA-1 antigen as a carbohydrate marker of human natural killer cells and immature lymphoid cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 255-261
Author(s):  
K Ohmori ◽  
T Yoneda ◽  
G Ishihara ◽  
K Shigeta ◽  
K Hirashima ◽  
...  
Keyword(s):  
B Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Normal Peripheral Blood ◽  
Cell Lineages ◽  
Human Lymphoid Cell ◽  
Wide Range

The distribution of a carbohydrate antigen, the sialyl SSEA-1 (sialyl Lex-i), in human lymphoid cells was investigated by flow cytometry with a specific monoclonal antibody, MoAb FH-6. We concluded that the lymphocytes positive for the sialyl SSEA-1 antigen present in normal peripheral blood (PB) are natural killer (NK) cells since the positive cells had an NK activity toward K562 cells, and most of the sialyl SSEA- 1+ cells were simultaneously positive for Leu-11 (CD-16) and Leu-19. Essentially, no T and B cells, defined by Leu-4 (CD3) and Leu-16 (CD20), were positive for the sialyl SSEA-1 antigen in PB samples taken from healthy donors and patients with disorders unrelated to lymphoid malignancies. Among the malignant lymphoid cells, many sialylated SSEA- 1+ cells were observed in large granular lymphocyte (LGL) leukemia cells and some acute lymphoblastic leukemia (ALL) blasts, but not in CLL cells or malignant lymphoma cells. Sialyl SSEA-1 was also positive in some cultured human lymphoid cell lines. We conclude that expression of the sialyl SSEA-1 antigen is strictly limited to a distinct population of NK cells among the mature lymphocytes in normal PB, but the antigen is present in a wide range of immature lymphoblasts of T- and B-cell lineages as well as the NK-cell lineage. The sialyl SSEA-1 antigen disappears from the surface of immature lymphocytes of T- and B- cell lineages during the course of maturation.

Hobit confers tissue-dependent programs to type 1 innate lymphoid cells

2021 ◽  
Vol 118 (50) ◽  
pp. e2117965118
Author(s):  
Kentaro Yomogida ◽  
Tarin M. Bigley ◽  
Tihana Trsan ◽  
Susan Gilfillan ◽  
Marina Cella ◽  
...  
Keyword(s):  
Viral Infection ◽  
Nk Cells ◽  
Salivary Glands ◽  
Intestinal Mucosa ◽  
Nk Cell ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Unique Cell ◽  
The Impact

Identification of type 1 innate lymphoid cells (ILC1s) has been problematic. The transcription factor Hobit encoded by Zfp683 has been proposed as a major driver of ILC1 programs. Using Zfp683 reporter mice, we showed that correlation of Hobit expression with ILC1s is tissue- and context-dependent. In liver and intestinal mucosa, Zfp683 expression correlated well with ILC1s; in salivary glands, Zfp683 was coexpressed with the natural killer (NK) master transcription factors Eomes and TCF1 in a unique cell population, which we call ILC1-like NK cells; during viral infection, Zfp683 was induced in conventional NK cells of spleen and liver. The impact of Zfp683 deletion on ILC1s and NK cells was also multifaceted, including a marked decrease in granzyme- and interferon-gamma (IFNγ)–producing ILC1s in the liver, slightly fewer ILC1s and more Eomes+ TCF1+ ILC1-like NK cells in salivary glands, and only reduced production of granzyme B by ILC1 in the intestinal mucosa. NK cell–mediated control of viral infection was unaffected. We conclude that Hobit has two major impacts on ILC1s: It sustains liver ILC1 numbers, while promoting ILC1 functional maturation in other tissues by controlling TCF1, Eomes, and granzyme expression.

scholarly journals Sialyl SSEA-1 antigen as a carbohydrate marker of human natural killer cells and immature lymphoid cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 255-261 ◽  
Author(s):  
K Ohmori ◽  
T Yoneda ◽  
G Ishihara ◽  
K Shigeta ◽  
K Hirashima ◽  
...  
Keyword(s):  
B Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Normal Peripheral Blood ◽  
Cell Lineages ◽  
Human Lymphoid Cell ◽  
Wide Range

Abstract The distribution of a carbohydrate antigen, the sialyl SSEA-1 (sialyl Lex-i), in human lymphoid cells was investigated by flow cytometry with a specific monoclonal antibody, MoAb FH-6. We concluded that the lymphocytes positive for the sialyl SSEA-1 antigen present in normal peripheral blood (PB) are natural killer (NK) cells since the positive cells had an NK activity toward K562 cells, and most of the sialyl SSEA- 1+ cells were simultaneously positive for Leu-11 (CD-16) and Leu-19. Essentially, no T and B cells, defined by Leu-4 (CD3) and Leu-16 (CD20), were positive for the sialyl SSEA-1 antigen in PB samples taken from healthy donors and patients with disorders unrelated to lymphoid malignancies. Among the malignant lymphoid cells, many sialylated SSEA- 1+ cells were observed in large granular lymphocyte (LGL) leukemia cells and some acute lymphoblastic leukemia (ALL) blasts, but not in CLL cells or malignant lymphoma cells. Sialyl SSEA-1 was also positive in some cultured human lymphoid cell lines. We conclude that expression of the sialyl SSEA-1 antigen is strictly limited to a distinct population of NK cells among the mature lymphocytes in normal PB, but the antigen is present in a wide range of immature lymphoblasts of T- and B-cell lineages as well as the NK-cell lineage. The sialyl SSEA-1 antigen disappears from the surface of immature lymphocytes of T- and B- cell lineages during the course of maturation.

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