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CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection

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Abstract

Defects in human leukocyte antigen (HLA) class I expression may allow tumor cells to escape immune recognition. T cell infiltration is associated with a good prognosis in many cancers. However, the role of HLA class I expression and tumor-infiltrating lymphocytes (TILs) in malignant pleural mesothelioma (MPM) has not been fully analyzed. In the present study, we investigated the immune profiles and conducted outcome analyses of MPM patients. HLA class I expression and TILs (CD4+, CD8+, and NK cells) were detected by immunohistochemistry in a series of 44 MPM cases. To detect HLA class I expression, specimens were stained with the anti-pan HLA class I monoclonal antibody EMR8-5. The expression of HLA class I was positive in all patients. There was no case that showed negative HLA class I expression. The density of CD4+ and CD8+ TILs were strongly correlated (R = 0.76, p < 0.001). A high density of CD8+ TILs was a significantly better prognostic factor for the survival of patients with extrapleural pneumonectomy (p < 0.05). Multivariate analysis revealed that a high density of CD8+ TILs is an independent prognostic factor for patients who underwent extrapleural pneumonectomy. The presence of intratumoral CD8+ T cells was correlated with an improved clinical outcome, raising the possibility that CD8+ T cells might play a pivotal role in the antitumor immune response against MPMs. Thus, the stimulation of CD8+ lymphocytes might be an efficacious immunotherapy for MPM patients.

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Abbreviations

HLA:

Human leukocyte antigen

TILs:

Tumor-infiltrating lymphocytes

MPM:

Malignant pleural mesothelioma

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Acknowledgments

We are grateful to Dr Koichi Yamazaki, former associate professor of the First Department of Medicine, Hokkaido University School of Medicine, for his outstanding support. This study was supported by Grant-in-Aid from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan

    Noriyuki Yamada, Satoshi Oizumi, Eiki Kikuchi, Naofumi Shinagawa, Jun Konishi-Sakakibara & Masaharu Nishimura

  2. Department of Internal Medicine, Kin-Ikyo Chuo Hospital, Sapporo, Japan

    Atsushi Ishimine

  3. Department of Medical Oncology and Clinical Research, NHO Yamaguchi-Ube Medical Center, Ube, Japan

    Keisuke Aoe

  4. Department of Respiratory Medicine, Okayama Rosai Hospital, Okayama, Japan

    Kenichi Gemba & Takumi Kishimoto

  5. Department of Pathology 1, Sapporo Medical University School of Medicine, Sapporo, Japan

    Toshihiko Torigoe

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  1. Noriyuki Yamada
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  2. Satoshi Oizumi
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Correspondence to Satoshi Oizumi.

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Yamada, N., Oizumi, S., Kikuchi, E. et al. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother 59, 1543–1549 (2010). https://doi.org/10.1007/s00262-010-0881-6

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  • DOI: https://doi.org/10.1007/s00262-010-0881-6

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