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

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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.

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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

ALC:

Absolute lymphocyte count

CIITA:

Class II transactivator

CTL:

Cytotoxic T cell

DLBCL:

Diffuse large B cell lymphoma

FFPE:

Formalin-fixed paraffin embedded

FISH:

Fluorescent in situ hybridization

HLA:

Human leukocyte antigen

HR:

Hazard ratio

IHC:

Immunohistochemistry

LOH:

Loss of heterozygosity

OS:

Overall survival

PFS:

Progression-free survival

R-CHOP:

RTX plus doxorubicin, cyclophosphamide, vincristine, and prednisolone

RTX:

Rituximab

TAA:

Tumor-associated antigen

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Acknowledgments

We thank all patients, physicians, nurses, and staff members who supported this analysis. This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (Clinical Cancer Research 22-014, 22-031 and 23-014), the National Cancer Center Research and Development Fund (21-6-3, 20-1, 23-A-23, 23-C-7, 26-A-4 and 26-A-24), and the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (25461442 and 16K09865).

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Author notes

  1. Kohei Tada

    Present address: Immunotherapy and Cell Therapy Service, St. Luke’s International Hospital, Tokyo, Japan

  2. Takashi Watanabe

    Present address: Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Tsu, Japan

Authors and Affiliations

  1. Department of Hematology and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Kohei Tada, Nobuhiko Yamauchi, Dai Maruyama, Sung-Won Kim, Takashi Watanabe, Kensei Tobinai & Yukio Kobayashi

  2. Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan

    Kohei Tada & Naoyuki Katayama

  3. Immunotherapy and Cell Therapy Service, St. Luke’s International Hospital, Tokyo, Japan

    Yuji Heike

  4. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan

    Akiko Miyagi Maeshima & Nobuyoshi Hiraoka

  5. Immunotherapy Research Field, Translational Research Group, and Translational Medicine Department, Phase 1 Group, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Tokyo, Japan

    Yuji Heike

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  1. Kohei Tada
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Corresponding author

Correspondence to Yukio Kobayashi.

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The authors have no conflicts of interest to declare. This research was approved by the Institutional Review Board of the National Cancer Center (2014-185).

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Tada, K., Maeshima, A.M., Hiraoka, N. et al. Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy. Cancer Immunol Immunother 65, 1213–1222 (2016). https://doi.org/10.1007/s00262-016-1883-9

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  • DOI: https://doi.org/10.1007/s00262-016-1883-9

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