Local production of the chemokines CCL5 and CXCL10 attracts CD8+ T lymphocytes into esophageal squamous cell carcinoma.

Jinyan Liu,Feng Li,Yi Zhang,Ling Cao,Liping Wang,Dan Wang,Xinfeng Chen,Song Zhao,Bing Li,Yu Ping,Pawel Kalinski,Stephen H Thorne,Bin Zhang

doi:10.18632/oncotarget.4617

Abstract

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.

Highlights

Chemokines are small heparin-binding proteins weighing 8–14 kDa, which guide the migration of circulating lymphocytes to specific tissues [1]
Our findings show that CCL5CCR5 and CXCL10-CXCR3 axes are critical for tumordirected movement of CD8+ T lymphocytes in esophageal squamous cell carcinoma (ESCC)
Several studies have examined the expression of chemokine receptors by esophageal carcinoma cells [25, 26], the expressions of ESCC-associated chemokines in relation to local T lymphocytes accumulation had not been investigated

Summary

Introduction

Chemokines are small heparin-binding proteins weighing 8–14 kDa, which guide the migration of circulating lymphocytes to specific tissues [1]. Chemokines induce the movement of lymphocytes in a concentration-dependent manner [2]. The immune cell-infiltration is tightly associated with chemotaxis, and the numbers and types of lymphocytes recruited are determined by the local chemokines secreted [3]. CCL5 and CXCL10 attract CD8+ T lymphocytes into various tumors [4,5,6,7]. Reported that CCL5 and CXCL10 favor the recruitment of CD8+ T lymphocytes into malignant tissues. The expression of CCL5 and CXCL10 and its impact on the migration of CD8+ T lymphocytes remain unknown in patients with esophageal squamous cell carcinoma (ESCC)

Methods

Results

Conclusion