Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses

Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.

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Faculty Opinions recommendation of Interferon and IL-27 antagonize the function of group 2 innate lymphoid cells and type 2 innate immune responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725957335.793513867 ◽

2016 ◽

Author(s):

Toshihiro Nakajima ◽

Hidetoshi Fujita

Keyword(s):

Immune Responses ◽

Innate Lymphoid Cells ◽

Innate Immune ◽

Lymphoid Cells ◽

Innate Immune Responses ◽

Group 2

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Faculty Opinions recommendation of Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727549021.793550895 ◽

2018 ◽

Author(s):

Sebastian Stintzing

Keyword(s):

Overall Survival ◽

Colorectal Carcinoma ◽

Final Analysis ◽

Line Treatment ◽

Metastatic Colorectal Carcinoma ◽

First Line ◽

First Line Treatment

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Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study

ESMO Open ◽

10.1016/j.esmoop.2021.100062 ◽

2021 ◽

Vol 6 (2) ◽

pp. 100062

Author(s):

J. Sastre ◽

P. García-Alfonso ◽

J.M. Viéitez ◽

M.T. Cano ◽

F. Rivera ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Phase Ii ◽

Tumour Cells ◽

Circulating Tumour Cells ◽

Wild Type ◽

Metastatic Colorectal Carcinoma ◽

First Line ◽

Pik3ca Mutations ◽

First Line Therapy ◽

Line Therapy

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The Cost Study of First- line Treatment of Metastatic Colorectal Carcinoma with Bevacizumab- containing Regimen in the Czech Republic

Klinicka onkologie ◽

10.14735/amko2014255 ◽

2014 ◽

Vol 27 (4) ◽

pp. 255-260

Author(s):

Irena Hradecká ◽

Barbora Říhová ◽

Renata Horová ◽

Regina Demlová

Keyword(s):

Czech Republic ◽

Colorectal Carcinoma ◽

Line Treatment ◽

Metastatic Colorectal Carcinoma ◽

First Line ◽

Cost Study ◽

The Czech Republic ◽

The Cost ◽

First Line Treatment

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STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn’s Disease

Journal of Immunology Research ◽

10.1155/2019/9406146 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ying Tang ◽

Sanda A. Tan ◽

Atif Iqbal ◽

Jian Li ◽

Sarah C. Glover

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Immune Responses ◽

Tyrosine Phosphorylation ◽

Innate Lymphoid Cells ◽

Immune Defense ◽

Lymphoid Cells ◽

Dependent Manner ◽

Regulatory Pathways ◽

Innate Effector

Crohn’s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele “A” with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 “A” risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse.

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Impact of prophylactic systemic antibiotics (SA) on outcome of patients (pts) with RAS-wildtype (RAS-wt) metastatic colorectal carcinoma (mCRC) treated with cetuximab-based first-line therapy. Subgroup analysis of the german non-interventional study ERBITAG

Annals of Oncology ◽

10.1093/annonc/mdz246.053 ◽

2019 ◽

Vol 30 ◽

pp. v218

Author(s):

S.W. Sahm ◽

M.-O. Zahn ◽

C. Maintz ◽

T. Goehler ◽

J. Janssen ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Subgroup Analysis ◽

Metastatic Colorectal Carcinoma ◽

First Line ◽

Interventional Study ◽

First Line Therapy ◽

Line Therapy ◽

Systemic Antibiotics

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2019 ATVB Plenary Lecture

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.119.312287 ◽

2020 ◽

Vol 40 (4) ◽

pp. 853-864 ◽

Cited By ~ 3

Author(s):

Tian X. Zhao ◽

Stephen A. Newland ◽

Ziad Mallat

Keyword(s):

Cardiovascular Disease ◽

T Cells ◽

Regulatory T Cells ◽

Immune Responses ◽

Interleukin 2 ◽

Cell Types ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Myocardial Repair

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.

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