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Updated: May 21, 2025
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Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
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An intraepithelial ILC1-like natural killer cell subset produces IL-13
Sainiteesh Maddineni1, Krishna Sharma1, Imran A Mohammad1
1Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, United States.
Frontiers in Immunology
|March 21, 2025
Summary
Researchers discovered a new subpopulation of Natural Killer (NK) cells in head and neck cancers. These cells, identified as intraepithelial ILC1-like NK cells, surprisingly produce IL-13 alongside IFNγ, suggesting novel therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Natural killer (NK) cells are crucial innate immune cells with significant antitumor activity.
- Intraepithelial ILC1 (ieILC1)-like NK cells, a subset of cytotoxic innate lymphoid cells, reside in tumor microenvironments, including head and neck squamous cell carcinomas (HNSCC).
- These ieILC1-like NK cells are known for their cytolytic functions and production of type 1 cytokines like IFNγ.
Purpose of the Study:
- To investigate the heterogeneity within the ieILC1-like NK cell population.
- To identify novel functional characteristics and cytokine production profiles of ieILC1-like NK cells in HNSCC.
- To explore the potential therapeutic implications of newly identified ieILC1-like NK cell subsets.
Main Methods:
- Ex vivo differentiation and stimulation of ieILC1-like NK cells.
- Co-culture experiments with HNSCC cell lines.
- Analysis of cytokine production (IFNγ and IL-13) using functional assays.
- Transcriptional profiling to confirm ILC1 signature.
- Identification of cells within tumor-infiltrating lymphocytes from HNSCC patients.
Main Results:
- A subpopulation of ex vivo differentiated ieILC1-like NK cells was identified that produces IL-13 upon stimulation.
- These IL-13-producing cells co-expressed IFNγ and maintained an ILC1 transcriptional signature.
- IL-13 production was induced by co-culture with tumor cells or by TGF-β and IL-15.
- IL-13-expressing ieILC1-like NK cells were found within tumor-infiltrating lymphocytes from HNSCC patients, confirming their in vivo presence.
- This demonstrates plasticity within the ieILC1-like NK cell population, with ILC1-like cells expressing a type 2 cytokine.
Conclusions:
- The ieILC1-like NK cell population exhibits greater heterogeneity than previously understood.
- A subset of ILC1-like NK cells can express IL-13, a type 2 cytokine, while retaining an ILC1 transcriptional profile.
- The presence of IL-13-producing ieILC1-like NK cells in HNSCC tumors suggests a role in cancer cell growth and immunoregulation.
- These findings highlight a potential new avenue for therapeutic manipulation in HNSCC treatment.
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