Intratumoral regulatory T cells are associated with suppression of colorectal carcinoma metastasis after resection through overcoming IL-17 producing T cells.
With opposite immune activities, regulatory T cells (Tregs) and IL-17 producing T cells were accumulated in various malignant tumors and played critical roles in pathophysiologic course of these diseases. In this study, we investigated the mix-effect of the intratumoral Tregs and IL-17 producing T cells on metastasis of colorectal carcinoma (CRC) after resection. The frequency of intratumoral Tregs and IL-17A+ T cells, and the levels of FoxP3 and IL-17 mRNA were analyzed. The ratio of Tregs/IL-17A+T cells and the ratio of FoxP3 mRNA/IL-17 mRNA were calculated. The activities of matrix metalloproteases (MMPs) in tumor tissues were analyzed. Meanwhile, Tregs from patient's blood was co-cultured with human CRC cells in the presence of IL-17. MMPs protein and mRNA levels were determined after 48 or 24h incubation. We found that Tregs and IL-17A+T cells were accumulated in CRC. The ratio of Tregs/IL-17A+T cells was decreased in CRC tissues. More intratumoral Tregs and less IL-17A+T cells were associated with suppressed MMPs activities and decreased metastases score. In addition, vitro studies demonstrated that Tregs suppressed MMPs expression in the presence of IL-17. Our findings suggested the possibility that intratumoral Tregs protected against metastasis of CRC after resection through overcoming IL-17 producing T cells.
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Quanrongzi
Q
Wang
Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Min
M
Feng
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Tongfu
T
Yu
Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. Electronic address: qingxin2121@yahoo.com.cn.
Xisheng
X
Liu
Department of General Surgery, The Second Affiliated Hospital of Yangzhou University Medical School, Yangzhou, China. Electronic address: yzu.edu.pjz@163.com.
Peijian
P
Zhang
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000951:Antigens, Neoplasm; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17
Colorectal carcinoma; IL-17; Matrix metalloproteases; Regulatory T cells