Loss of HLA-DR expression is related to tumor microenvironment and predicts adverse outcome in diffuse large B-cell lymphoma

Abstract

The interaction between tumor cells and the tumor microenvironment is essential in the development and progression of diffuse large B-cell lymphoma (DLBCL). Loss of human leukocyte antigen DR (HLA-DR) in DLBCL is a robust adverse prognostic marker. We evaluated the immunohitochemical expression of HLA-DR in lymphoma and the biologic implications of the loss of HLA-DR. The loss of HLA-DR correlated with clinical stage (p < 0.05), International Prognosis Index (p < 0.05), soluble interleukin-2 receptor (p < 0.05) and poor outcome in patients with DLBCL, especially among elderly patients. Flow cytometry analysis of the infiltrating T-cells showed that the mean CD4 + CD25 +/CD8 ratio of the infiltrating T-cells was higher in the HLA-DR positive group than in the HLA-DR negative group (p < 0.05). These data suggest that loss of HLA-DR expression in DLBCL decreases the ratio of helper T-cell within the T-cell population in the tumor microenvironment and might contribute to escape from immunosurveillance.

Keywords::

• Diffuse large B-cell lymphoma
• HLA-DR
• tumor microenvironment

Acknowledgements

We wish to thank T. Aoki, Y. Ohno, K. Ohsawa, T. Nakajo and K. Matsuno for technical assistance. This study was supported by JSPSS KAKENHI Grant, number 23590413 and Saitama Medical University Internal Grant, number 26-B1-03. All authors approved the final version of the manuscript and declare that they have no conflicts of interest and no competing financial interests.

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