Local production of the chemokines CCL5 and CXCL10 attracts CD8+ T lymphocytes into esophageal squamous cell carcinoma
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Jinyan Liu1,*, Feng Li1,*, Yu Ping1, Liping Wang2, Xinfeng Chen1, Dan Wang1, Ling Cao1, Song Zhao3, Bing Li3, Pawel Kalinski5, Stephen H. Thorne5, Bin Zhang6, Yi Zhang1,2,4
1Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
3Department of Thoracic surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China
4Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou, Henan, P.R. China
5Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA
6Robert H. Lurie Comprehensive Cancer Center, Department of Medicine-Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
*These authors have contributed equally to this work
Yi Zhang, e-mail: [email protected]
Keywords: esophageal squamous cell carcinoma, T lymphocyte, chemotaxis, CCL5, CXCL10
Received: April 01, 2015 Accepted: July 06, 2015 Published: July 16, 2015
Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with poor prognosis in China. Chemokines secreted by tumors are pivotal for the accumulation of CD8+ T lymphocytes within malignant lesions in several types of cancers, but the exact mechanism underlying CD8+ T lymphocyte homing is still unknown in ESCC. In this study, we revealed that, compared with marginal tissues, the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif) ligand 10 (CXCL10) was upregulated in ESCC tissues. CCL5 expression was positively associated with the overall survival of patients. Meanwhile, RT-PCR data showed that the expression of CCL5 and CXCL10 was positively correlated with the local expressions of the CD8+ T lymphocyte markers (CD8 and Granzyme B) in tumor tissues. Correspondingly, CD8+ T lymphocytes were more frequently CCR5- and CXCR3-positive in tumor than in peripheral blood. Transwell analysis showed both CCL5 and CXCL10 were important for the chemotactic movement of CD8+ T lymphocytes. Our data indicate that CCL5 and CXCL10 serve as the key chemokines to recruit CD8+ T lymphocytes into ESCC tissue and may play a role in patient survival.
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