TY - JOUR
T1 - Human NKp44+group 3 innate lymphoid cells associate with tumor-associated tertiary lymphoid structures in colorectal cancer
AU - Ikeda, Atsuyo
AU - Ogino, Takayuki
AU - Kayama, Hisako
AU - Okuzaki, Daisuke
AU - Nishimura, Junichi
AU - Fujino, Shiki
AU - Miyoshi, Norikatsu
AU - Takahashi, Hidekazu
AU - Uemura, Mamoru
AU - Matsuda, Chu
AU - Yamamoto, Hirofumi
AU - Takeda, Kiyoshi
AU - Mizushima, Tsunekazu
AU - Mori, Masaki
AU - Doki, Yuichiro
N1 - Funding Information:
This work was supported by a research grant from the Osaka Medical Research Foundation for Intractable Disease (to T. Ogino), PRIME, Japan Agency for Medical Research and Development (19gm6210016; to H. Kayama), JSPS KAKENHI Grant Number 17K10631 (to T. Mizushima), a research grant from the Princess Takamatsu Cancer Research Fund 18-25031 (to T. Mizushima), and Astellas Research Support (to T. Mizushima).
Publisher Copyright:
© 2020 American Association for Cancer Research Inc.. All rights reserved.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from patients with colorectal cancer, and the cells were isolated by enzymatic digestion. NKp44+ ILC3s with high expression of tertiary lymphoid structure (TLS) formation-related genes, including LTA, LTB, and TNF, accumulated in the normal colonic mucosa and T1/T2 tumors. However, the number of NKp44+ILC3s was significantly reduced in T3/T4 tumors compared with normal colonic mucosa and T1/T2 tumors. NKp44+ILC3s present in T3/T4 tumors had decreased expression of TLS formation-related genes, whereas stromal cells had decreased expression of CXCL13, CCL19, and CCL21. The decreasing number of NKp44+ILC3s during tumor progression correlated with the TLS density in tumors. Thus, our results indicate that NKp44+ILC3s infiltrate colorectal cancer tissue, but the number of cells decreases in T3/T4 tumors with associated decreases in TLS induction.
AB - Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from patients with colorectal cancer, and the cells were isolated by enzymatic digestion. NKp44+ ILC3s with high expression of tertiary lymphoid structure (TLS) formation-related genes, including LTA, LTB, and TNF, accumulated in the normal colonic mucosa and T1/T2 tumors. However, the number of NKp44+ILC3s was significantly reduced in T3/T4 tumors compared with normal colonic mucosa and T1/T2 tumors. NKp44+ILC3s present in T3/T4 tumors had decreased expression of TLS formation-related genes, whereas stromal cells had decreased expression of CXCL13, CCL19, and CCL21. The decreasing number of NKp44+ILC3s during tumor progression correlated with the TLS density in tumors. Thus, our results indicate that NKp44+ILC3s infiltrate colorectal cancer tissue, but the number of cells decreases in T3/T4 tumors with associated decreases in TLS induction.
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U2 - 10.1158/2326-6066.CIR-19-0775
DO - 10.1158/2326-6066.CIR-19-0775
M3 - Article
C2 - 32229590
AN - SCOPUS:85085903650
SN - 2326-6066
VL - 8
SP - 724
EP - 731
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 6
ER -
