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Activated innate lymphoid cell populations accumulate in human tumour tissues.

ABSTRACT: BACKGROUND:Innate lymphoid cells (ILC) are part of a heterogeneous family of haematopoietic effector cells which lack re-arranged antigen-specific receptors. They promote host defense and contribute to tissue and metabolic homeostasis, wound healing and immune surveillance. Their role in human cancer immunity is less defined, and therefore we aimed to identify the frequency and phenotype of distinct ILC groups in various types of cancer. METHODS:Tissue samples and peripheral blood were collected from patients undergoing surgical resection of gastrointestinal and breast tumours. Single cell suspension of tumour tissue was immediately obtained following surgery using tumour dissociation. RESULTS:We observed significantly higher frequencies of ILC2 (p value: 0.04) in malignant breast cancer tissue and significantly higher frequencies of group 1 ILC (p value: 0.001) in malignant gastrointestinal tumours. Tumour infiltrating ILC were found to show an activated phenotype with higher expression of MHC-II, KLRG1, early activation marker CD69 and CD44. CONCLUSIONS:Activated innate lymphoid cells infiltrate tumours dependent on tumour type and location.

SUBMITTER: Salimi M

PROVIDER: S-EPMC5870240 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Activated innate lymphoid cell populations accumulate in human tumour tissues.

Salimi Maryam M Wang Ruozheng R Yao Xuan X Li Xi X Wang Xiyan X Hu Yuhui Y Chang Xumei X Fan Peiwen P Dong Tao T Ogg Graham G

BMC cancer 20180327 1

<h4>Background</h4>Innate lymphoid cells (ILC) are part of a heterogeneous family of haematopoietic effector cells which lack re-arranged antigen-specific receptors. They promote host defense and contribute to tissue and metabolic homeostasis, wound healing and immune surveillance. Their role in human cancer immunity is less defined, and therefore we aimed to identify the frequency and phenotype of distinct ILC groups in various types of cancer.<h4>Methods</h4>Tissue samples and peripheral blood ...[more]

PMID: 29587679

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Project description:Background: Innate lymphoid cells (ILCs) have now been identified within most tissues of the body and current evidence indicates that this family of cells play a fundamental role in maintaining tissue homeostasis. However, few studies have compared the ILC populations between several tissues. Methods: We sought to generate a comprehensive characterisation of the ILC populations in different tissues of C57BL/6 WT and genetically modified mice targeting costimulatory pathways, using transcription factor expression to define specific groups. Results: Consistent with studies individually describing the ILC composition in different tissues, our analysis revealed different ILC groups dominate the ILC population in different tissues. Additionally, we observed a population of IL-7Rα +Id2 + cells lacking expression of lineage markers but also lacking expression of GATA-3, RORgt or T-bet. This population was most evident in ear skin where it outnumbered the defined ILC groups, however, further experiments demonstrated that detection of these cells was influenced by how the tissue was digested, raising concerns as to its real nature. Since both ILC2 and ILC3 express ICOS, we then investigated the requirement for ICOS:ICOSL interactions in the homeostasis of ILC populations at these sites. Surprisingly, no significant differences were detected in the number of ILC1, ILC2 or ILC3 between WT and ICOSL -/- mice in any tissue, indicating that this pathway is not required for ILC homeostasis at these sites. These data were compared with CD80 -/-CD86 -/- mice given evidence of CD28 expression by some ILC and ILC crosstalk with activated T cells. Notably, the absence of CD28 ligands resulted in a significant increase in ILC2 and ILC3 numbers in the intestine. Conclusions: Together, these data provide new insight into ILC composition in different tissues in both WT and genetically modified mice where key costimulatory pathways are genetically deleted, providing a useful resource for further research into ILC biology.

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Activated innate lymphoid cell populations accumulate in human tumour tissues.

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Activated innate lymphoid cell populations accumulate in human tumour tissues.

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