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B7-H3 Negatively Modulates CTL-Mediated Cancer Immunity.

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Author information

Affiliations

  • 1. Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
      Authors
    • Yonesaka K 1, 6
    • Haratani K 1
    • Sakai H 1
    • Kato R 1
    • Takegawa N 1
    • Takahama T 1
    • Tanaka K 1
    • Hayashi H 1
    • Takeda M 1
    • Nakagawa K 1
    (10 authors)
  • 2. Department of Immunology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
      Authors
    • Takamura S 2
    • Kato S 2
    • Miyazawa M 2
    (3 authors)
  • 3. Department of Pathology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
      Authors
    • Maenishi O 3
    (1 author)
  • 4. Department of Genome Biology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.
      Authors
    • Sakai K 4
    • Nishio K 4
    (2 authors)
  • 5. Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Osaka, Japan.
      Authors
    • Chiba Y 5
    (1 author)
    • Show all (10)

ORCIDs linked to this article

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 12 Mar 2018, 24(11):2653-2664
https://doi.org/10.1158/1078-0432.ccr-17-2852 PMID: 29530936 

Abstract 

Purpose: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed in various malignancies. To our knowledge, this study is the first to evaluate B7-H3 expression in NSCLCs treated with anti-PD-1 therapy and the therapeutic potential of a combination of anti-PD-1 therapy and B7-H3 targeting.Experimental Design: B7-H3 expression was evaluated immunohistochemically in patients with NSCLC (n = 82), and its relationship with responsiveness to anti-PD-1 therapy and CD8+ tumor-infiltrating lymphocytes (TILs) was analyzed. The antitumor efficacy of dual anti-B7-H3 and anti-programmed death ligand-1 (PD-L1) antibody therapy was evaluated using a syngeneic murine cancer model. T-cell numbers and functions were analyzed by flow cytometry.Results: B7-H3 expression was evident in 74% of NSCLCs and was correlated critically with nonresponsiveness to anti-PD-1 immunotherapy. A small number of CD8+ TILs was observed as a subpopulation with PD-L1 tumor proportion score less than 50%, whereas CD8+ TILs were still abundant in tumors not expressing B7-H3. Anti-B7-H3 blockade showed antitumor efficacy accompanied with an increased number of CD8+ TILs and recovery of effector function. CD8+ T-cell depletion negated antitumor efficacy induced by B7-H3 blockade, indicating that improved antitumor immunity is mediated by CD8+ T cells. Compared with a single blocking antibody, dual blockade of B7-H3 and PD-L1 enhanced the antitumor reaction.Conclusions: B7-H3 expressed on tumor cells potentially circumvents CD8+-T-cell-mediated immune surveillance. Anti-B7-H3 immunotherapy combined with anti-PD-1/PD-L1 antibody therapy is a promising approach for B7-H3-expressing NSCLCs. Clin Cancer Res; 24(11); 2653-64. ©2018 AACR.

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Read article at publisher's site: https://doi.org/10.1158/1078-0432.ccr-17-2852

Read article for free, from open access legal sources, via Unpaywall: https://figshare.com/articles/journal_contribution/Figure_S1_from_B7-H3_Negatively_Modulates_CTL-Mediated_Cancer_Immunity/22464527/1/files/39915851.pdfUnpaywall

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