Impact of T-cell receptor and B-cell receptor repertoire on the recurrence of early stage lung adenocarcinoma

Exp Cell Res. 2020 Sep 15;394(2):112134. doi: 10.1016/j.yexcr.2020.112134. Epub 2020 Jun 12.

Abstract

Surgical resection is the only curative treatment for patients with early stage non-small cell lung cancer. However, approximately 33% of non-small cell lung cancer patients recur with the stage I disease, which may be attributed to a deficiency in antitumor immunity. In the present study, for early stage lung adenocarcinoma patients with early recurrence and early non-recurrence, we investigated the quantity of tumor-infiltrating T and B cells by immunohistochemistry, as well as the genes in the complementarity determining region 3 of the T-cell receptor β chain and the B-cell receptor immunoglobulin heavy chain. A decreased number of tumor-infiltrating lymphocytes cells (CD3+, CD4+, CD8+ and CD20+) was present in early recurrence patients. A significant increase in oligoclones and a reduction in T-cell receptor diversity were observed in the early recurrence group. Furthermore, there was a preference for V, J gene, and VJ gene combinations in patients with early recurrence versus non-recurrence, suggesting that this may be a new biomarker for the recurrence of early stage lung adenocarcinoma. These data indicate that T and B cell receptor repertoires influence the depth of human adaptive immune responses, and in addition to the quantity of tumor infiltrating T and B cells, may contribute to the prevention of early stage lung adenocarcinoma recurrence after surgical resection. Our study illustrates the potential value of the immune repertoire for predicting clinical efficacy and patient outcomes.

Keywords: B-Cell receptor repertoire; Early recurrence; Non-small cell lung cancer; T-cell receptor repertoire; Tumor infiltrating lymphocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology*
  • B-Lymphocytes / immunology
  • Base Sequence
  • Clone Cells
  • Complementarity Determining Regions / genetics
  • Female
  • Genetic Variation
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / immunology

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell