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Intravital Imaging of Intraepithelial Lymphocytes in Murine Small Intestine
Published on: June 24, 2019
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Intraepithelial ILC1-Like NK Cells Increase Lymphocyte Infiltration into the Tumor Microenvironment via the CXCL10
Sainiteesh Maddineni1, Krishna Sharma1, Imran A Mohammad1
1Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, California, USA.
Summary
Intraepithelial type 1 innate lymphoid cells (ieILC1s) enhance T-cell infiltration into head and neck tumors by inducing CXCL10 production. These findings suggest ieILC1s may impact cancer immunotherapy efficacy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Intraepithelial type 1 innate lymphoid cells (ieILC1s) are lymphocytes residing in the tumor microenvironment of head and neck squamous cell carcinoma.
- The precise role of ieILC1s in modulating anti-tumor immunity, particularly T-cell trafficking, remains to be fully elucidated.
Purpose of the Study:
- To investigate the influence of ieILC1s on T-cell infiltration into head and neck tumors.
- To explore the mechanisms by which ieILC1s modulate the tumor microenvironment.
Main Methods:
- Generation of cytotoxic ieILC1-like cells from natural killer (NK) cells in vitro.
- Utilizing an in vivo tumor model to assess T-cell trafficking.
- Co-culture experiments to analyze cytokine production (CXCL10, IFNy) via flow cytometry and supernatant analysis.
Main Results:
- Intratumoral administration of ieILC1-like NK cells significantly increased T-cell infiltration into the tumor.
- Co-culture of ieILC1-like NK cells with tumor cells led to elevated CXCL10 levels in the supernatant.
- ieILC1-like NK cells produced IFNy, which induced tumor cells to produce CXCL10, a chemokine known to attract T cells.
Conclusions:
- ieILC1-like NK cells promote T-cell infiltration into the tumor microenvironment by inducing tumor cell production of the chemokine CXCL10.
- These findings highlight a novel mechanism by which ieILC1s contribute to the inflammatory landscape of head and neck tumors.
- Further investigation into the role of ieILC1s in response to immune checkpoint blockade is warranted.
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