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lncRNA - Long Non-coding RNAs02:39

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Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)
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Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal

Atsuyo Ikeda1, Takayuki Ogino2, Hisako Kayama3,4,5

  • 1Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

Cancer Immunology Research
|April 2, 2020
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Innate lymphoid cells (ILCs) are crucial for gut health and cancer immunity. In colorectal cancer, NKp44+ ILC3s decrease in advanced tumors, impacting tertiary lymphoid structures (TLS) and potentially tumor immunity.

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Area of Science:

  • Immunology
  • Oncology
  • Gastroenterology

Background:

  • Innate lymphoid cells (ILCs) play roles in tissue homeostasis and cancer.
  • The specific function of ILCs in colorectal cancer (CRC) remains unclear.
  • Understanding ILCs in the CRC tumor microenvironment is critical.

Purpose of the Study:

  • To characterize human ILCs in normal colon and CRC tissues.
  • To investigate the role of ILCs in the CRC tumor immune microenvironment.
  • To determine the relationship between ILCs, tertiary lymphoid structures (TLS), and CRC progression.

Main Methods:

  • Human normal colon and CRC tissues were obtained from patients.
  • Cells were isolated using enzymatic digestion.
  • NKp44+ ILC3s and their gene expression related to TLS formation were analyzed.

Main Results:

  • NKp44+ ILC3s expressing TLS formation genes (LTA, LTB, TNF) were found in normal mucosa and early-stage (T1/T2) CRC.
  • The number of NKp44+ ILC3s significantly decreased in advanced (T3/T4) CRC.
  • Advanced CRC showed reduced expression of TLS-related genes in NKp44+ ILC3s and stromal cells (CXCL13, CCL19, CCL21).
  • Decreased NKp44+ ILC3s correlated with reduced TLS density in tumors.

Conclusions:

  • NKp44+ ILC3s infiltrate CRC tissues but decline in advanced stages.
  • The reduction in NKp44+ ILC3s is associated with decreased TLS formation in T3/T4 tumors.
  • These findings suggest a role for NKp44+ ILC3s and TLS in CRC progression and immune response.