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

Oncotarget. 2015 Sep 22;6(28):24978-89. 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.

Keywords: CCL5; CXCL10; T lymphocyte; chemotaxis; esophageal squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / metabolism*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Movement / genetics
  • Chemokine CCL5 / genetics*
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL10 / genetics*
  • Chemokine CXCL10 / metabolism
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Granzymes / genetics
  • Granzymes / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CD8 Antigens
  • Chemokine CCL5
  • Chemokine CXCL10
  • Granzymes