Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer

J Transl Med. 2015 Aug 27:13:279. doi: 10.1186/s12967-015-0647-1.

Abstract

Background: Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival.

Methods: A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging.

Results: A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95% CI 1.7-5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95% CI 1.4-5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95% CI 1.2-4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95% CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95% CI 0.42-0.85).

Conclusions: Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigen Presentation
  • Area Under Curve
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / mortality
  • Female
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Odds Ratio
  • Prognosis
  • Proportional Hazards Models
  • T-Lymphocytes, Cytotoxic / cytology
  • Tissue Array Analysis

Substances

  • Histocompatibility Antigens Class I
  • Membrane Transport Proteins
  • tapasin