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

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.

• Authors: Lena Sokol, Viktor H Koelzer, Tilman T Rau, Eva Karamitopoulou, Inti Zlobec, Alessandro Lugli
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 279 (Aug 27 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 26310568 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histocompatibility Antigens Class I
• Membrane Transport Proteins
• tapasin

Topics

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