Jing Wu1, Hang Cheng1,2, Helei Wang1,3, Guoxia Zang1, Lingli Qi1,4, Xinping Lv1, Chunyan Liu1,5, Shan Zhu1, Mingyou Zhang6, Jiuwei Cui7, Hideki Ueno8, Yong-Jun Liu9, Jian Suo3, Jingtao Chen1,10. 1. Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, China. 2. Department of Pediatrics, The First Hospital, Jilin University, Changchun, China. 3. Department of Stomach Colorectal Anal Surgery, The First Hospital, Jilin University, Changchun, China. 4. Department of Pediatric Gastroenterology, The First Hospital, Jilin University, Changchun, China. 5. Department of Gynecology, The First Hospital, Jilin University, Changchun, China. 6. Department of Cardiovascular Center, The First Hospital, Jilin University, Changchun, China. 7. Cancer Center, The First Hospital, Jilin University, Changchun, China. 8. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 9. Department of Research and Development of Sanofi, Cambridge, MA, United States. 10. Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Abstract
Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1-induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in human colon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancer patients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.
Background: Innate lymphoid cells (ILCs), so far studied mostly in mouse models, are important tissue-resident innate immune cells that play important roles in the colorectal cancer microenvironment and maintain mucosal tissue homeostasis. Plasmacytoid dendritic cells (pDCs) present complexity in various tumor types and are correlated with poor prognosis. pDCs can promote HIV-1-induced group 3 ILC (ILC3) depletion through the CD95 pathway. However, the role of ILC3s in humancolon cancer and their correlation with other immune cells, especially pDCs, remain unclear. Methods: We characterized ILCs and pDCs in the tumor microenvironment of 58 colon cancerpatients by flow cytometry and selected three patients for RNA sequencing. Results: ILC3s were negatively correlated, and pDCs were positively correlated, with cancer pathological stage. There was a negative correlation between the numbers of ILC3s and pDCs in tumor tissues. RNA sequencing confirmed the correlations between ILC3s and pDCs and highlighted the potential function of many ILC- and pDC-associated differentially expressed genes in the regulation of tumor immunity. pDCs can induce apoptosis of ILC3s through the CD95 pathway in the tumor-like microenvironment. Conclusions: One of the interactions between ILC3s and pDCs is via the CD95 pathway, which may help explain the role of ILC3s in colon cancer.
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