Characteristics of Tumor Infiltrating Lymphocyte and Circulating Lymphocyte Repertoires in Pancreatic Cancer by the Sequencing of T Cell Receptors

Sci Rep. 2015 Sep 2:5:13664. doi: 10.1038/srep13664.

Abstract

Pancreatic cancer has a poor prognosis and few effective treatments. The failure of treatment is partially due to the high heterogeneity of cancer cells within the tumor. T cells target and kill cancer cells by the specific recognition of cancer-associated antigens. In this study, T cells from primary tumor and blood of sixteen patients with pancreatic cancer were characterized by deep sequencing. T cells from blood of another eight healthy volunteers were also studied as controls. By analyzing the complementary determining region 3 (CDR3) gene sequence, we found no significant differences in the T cell receptor (TCR) repertoires between patients and healthy controls. Types and length of CDR3 were similar among groups. However, two clusters of patients were identified according to the degree of CDR3 overlap within tumor sample group. In addition, clonotypes with low frequencies were found in significantly higher numbers in primary pancreatic tumors compared to blood samples from patients and healthy controls. This study is the first to characterize the TCR repertoires of pancreatic cancers in both primary tumors and matched blood samples. The results imply that specific types of pancreatic cancer share potentially important immunological characteristics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Clone Cells
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Sequence Analysis, Protein*

Substances

  • Complementarity Determining Regions
  • RNA, Messenger
  • Receptors, Antigen, T-Cell