Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma

Duan, Jingjing1; Wang, Haotian1; Liu, Minglu2; Chen, Yin3; Li, Ning1; Liu, Jieqiong2; Wang, Lingxiong2; Li, Lin3; Liu, Yaru3; Dong, Pengfei3; Wang, Xiuxuan3; Fan, Zhongyi4; Jiao, Shunchang2

2024-08-01

10.21147/j.issn.1000-9604.2024.04.01

CHINESE JOURNAL OF CANCER RESEARCH   影响因子和分区

1000-9604

1993-0631

Objective: CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated. Methods: Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and in vitro experiments were then performed. Results: DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro. Conclusions: Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.

CD8+T cells DEFB1 dendritic cells esophageal squamous cell carcinoma tumor immune microenvironment

SCI

英语

通讯

National Natural Science Foundation of China["81972681","82103677"] ; Tianjin Education Commission Research Plan Project[2021KJ201] ; Shenzhen High-level Hospital Construction Fund[G2022139] ; Tianjin Key Medical Discipline (Specialty) Construction Project[TJYXZDXK-009A]

Oncology

Oncology

WOS:001303628800001

CHINESE JOURNAL CANCER RESEARCH CO

Web of Science

1.Tianjin Med Univ Canc Inst & Hosp, Tianjins Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin Key Lab Digest Canc,Natl Clin Res Ctr Can, Tianjin 300060, Peoples R China
2.Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Oncol, Beijing 100039, Peoples R China
3.Beijing DCTY Biotech Co LTD, Beijing 102200, Peoples R China
4.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Hosp 2, Dept Biotherapy Ctr, Shenzhen 518112, Peoples R China

Duan, Jingjing,Wang, Haotian,Liu, Minglu,et al. Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma[J]. CHINESE JOURNAL OF CANCER RESEARCH,2024,36(4).

Duan, Jingjing.,Wang, Haotian.,Liu, Minglu.,Chen, Yin.,Li, Ning.,...&Jiao, Shunchang.(2024).Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma.CHINESE JOURNAL OF CANCER RESEARCH,36(4).

Duan, Jingjing,et al."Tumor-derived DEFB1 induces immune tolerance by inhibiting maturation of dendritic cell and impairing CD8+T cell function in esophageal squamous cell carcinoma".CHINESE JOURNAL OF CANCER RESEARCH 36.4(2024).