Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy

Cancer Immunol Immunother. 2016 Oct;65(10):1213-22. doi: 10.1007/s00262-016-1883-9. Epub 2016 Aug 13.

Abstract

Loss of tumor cell human leukocyte antigen (HLA) is an immune escape mechanism for malignancies. However, the effect of low HLA class I or class II expression in diffuse large B cell lymphoma (DLBCL) treated with chemoimmunotherapy with the monoclonal antibody rituximab is largely unknown. We retrospectively analyzed samples and other data from 144 patients with DLBCL who were newly diagnosed in our institution and treated with standard R-CHOP therapy. We used antibodies against pan-HLA class I and pan-HLA class II molecules to assess HLA expression and its effect on prognosis. In a multivariate analysis, loss of HLA class II expression was a significantly independent adverse factor for progression-free survival (PFS; hazard ratio 2.3; 95 % confidence interval 1.2-4.6; P = 0.01). Although HLA class I loss of expression did not correlate with prognosis, the combination of HLA class I(+) with either low peripheral lymphocyte count or CD3(+) lymphocyte count was an adverse prognostic factor for PFS. Loss of HLA class II is an International Prognostic Index (IPI)-independent adverse factor for PFS in patients with DLBCL treated with standard therapy. However, in contrast to other solid cancers, HLA class I loss was not solely a prognostic factor in DLBCL.

Keywords: Absolute lymphocyte count; CD3 count; Human leukocyte antigen (HLA); Prognosis; Rituximab (RTX).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Combined Chemotherapy Protocols
  • Cyclophosphamide
  • Doxorubicin
  • Female
  • Follow-Up Studies
  • HLA Antigens / metabolism*
  • Histocompatibility Antigens Class I / metabolism*
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Immunohistochemistry / methods*
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prednisone
  • Prognosis
  • Rituximab
  • Survival Analysis
  • Tumor Escape
  • Vincristine
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone