Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity.

By F. Hirano, K. Kaneko, H. Tamura, Haidong Dong, Shengdian Wang, Masao Ichikawa, C. Rietz, D. Flies, J. Lau, G. Zhu and 2 more. Cancer Research, 2005

1,038 citations recorded by the source corpus.

Contemporary approaches for vaccination and immunotherapy are often capable of eliciting strong T-cell responses against tumor antigens. However, such responses are not parallel to clinical tumor regression. The development of evasion mechanisms within tumor microenvironment may be responsible for poor therapeutic responses. We report here that constitutive or inducible expression of B7-H1, a B7 family molecule widely expressed by cancers, confers resistance to therapeutic anti-CD137 antibody in mice with established tumors. The resistance is accompanied with failure of antigen-specific CD8+ CTLs to destroy tumor cells without impairment of CTL function. Blockade of B7-H1 or PD-1 by specific monoclonal antibodies could reverse this resistance and profoundly enhance therapeutic efficacy. Our findings support that B7-H1/PD-1 forms a molecular shield to prevent destruction by CTLs and implicate new approaches for immunotherapy of human cancers.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/b729127d598b10450f71508504163cb9e764c86d

How researchers see this paper

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In Immunology

1. D. Pardoll
2. Lieping Chen
3. E. Wherry
4. G. Freeman
5. Arlene H. Sharpe
6. W. Zou
7. Kristen E. Pauken
8. S. Topalian

In Oncology

1. D. Pardoll
2. Lieping Chen
3. E. Wherry
4. G. Freeman
5. Arlene H. Sharpe
6. W. Zou
7. Kristen E. Pauken
8. S. Topalian

Citations in the corpus

• Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. (2015, positive): “This discrepancy was explained by the finding that IFN-γ upregulates PD-L1 on the cell surface of normal tissues and in various tumor lines (7, 17, 19).”
• Mechanisms of immune evasion by tumors. (2006, background): “In recent data, this observation has been confirmed in murine tumor models, where blockade of either PD1 or of the PD1 ligand B7‐H1 potentiates an antitumor immune response (Hirano et al., 2005).”
• Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma (2013, background): “The relevance of the PD-1:PD-L1 checkpoint in cancer immunity is highlighted by reports demonstrating that blockade of PD-L1 or PD-1 by specific mAbs can reverse the anergic state of tumorspecific T cells and thereby enhance antitumor immunity (10-11, 26-27).”
• Inhibitory B7-family molecules in the tumour microenvironment (2008, background): “Injection of an antibody specific for B7-H1 increased T-cell immunity and induced tumour regressio”
• PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity (2017, background): “Our work extends this finding into the tumor microenvironment, and supports the concept of PD-L1 acting as a molecular shield on tumor cells to prevent cytolysis mediated by T cells (Iwai et al., 2002; Rodig et al., 2003; Hirano et al., 2005; Azuma et al., 2008).”
• Prostate cancer and inflammation: the evidence (2012, background): “A number of human tumours have been found to express PD-1L (B7H1),(92) and expression of PD-1 on cytotoxic T lymphocytes (CTL) inhibits antitumour effector function.(93) Very promising results are arising from clinical trials based on treatment strategies utilizing monoclonal antibodies for PD-1 blo”
• PD-L1 regulates the development, maintenance, and function of induced regulatory T cells (2009, neutral): “…in several cancers (Dong et al., 2002; Iwai et al., 2002; Strome et al., 2003; Konishi et al., 2004; Thompson et al., 2004; Blank et al., 2005; Hirano et al., 2005; Ohigashi et al., 2005; Dorfman et al., 2006; Wu et al., 2006; Inman et al., 2007; Nakanishi et al., 2007; Nomi et al., 2007;…”
• Overcoming T cell exhaustion in infection and cancer (2015, background): “In many mouse tumor systems, PD-1 pathway blockade is often administered early at time points when full exhaustion may not yet have developed [12, 13, 36, 117, 120].”
• IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer (2015, background): “Although PDL1 is known to suppress cytotoxic activity of CTLs (Iwai et al, 2002; Hirano et al, 2005; Abiko et al, 2013), function of TILs was similar regardless of different expression status of PD-L1 on tumour cells (data not shown), probably because TIL function is inevitably suppressed by…”