期刊论文详细信息
Journal for ImmunoTherapy of Cancer
The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer: unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors
Pedro Romero1  Emanuela Romano1 
[1] Department of Oncology, Ludwig Cancer Research Center, University Hospital of Lausanne, Lausanne, Switzerland
关键词: Cancer;    Checkpoint blockade;    PD-1;    Immunotherapy;   
Others  :  1175251
DOI  :  10.1186/s40425-015-0059-z
 received in 2015-03-04, accepted in 2015-03-16,  发布年份 2015
PDF
【 摘 要 】

The role of immune checkpoints in modulating the magnitude as well as the functional profile of T cell responses is increasingly understood in molecular detail. Antibody-mediated blockade of co-inhibitory receptors has been shown to restore T cell function in both chronic viral infections and cancer. The latter has been successfully translated to new therapeutic options in the treatment of cancer. Indeed, monoclonal antibodies blocking either CTLA-4 or PD-1 have recently been approved for the treatment of metastatic melanoma in the United States, Europe and Japan. In this commentary, we summarize and put into perspective five letters recently published back to back in the November 27 (2014) issue of Nature reporting on different immunological and clinical aspects of blockade of the PD-1/PD-L1 pathway in tumor bearing hosts. Notably, treatment with anti-PD-L1 blocking antibody was shown result in profound clinical responses in patients with several solid tumor including bladder, lung and head and neck carcinomas among others. These five simultaneous publications highlight the tremendous therapeutic potential of targeting the PD-1/PD-L1 immune checkpoint and emphasize the need to identify appropriate biomarkers to guide their optimal clinical application.

【 授权许可】

   
2015 Romano and Romero; licensee BioMed Central.

【 预 览 】
附件列表
Files Size Format View
20150427091512300.pdf 363KB PDF download
【 参考文献 】
  • [1]Pardoll DM: The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer 2012, 12(4):252-64.
  • [2]Herbst RS, et al.: Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014, 515(7528):563-7.
  • [3]Powles T, et al.: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014, 515(7528):558-62.
  • [4]Tumeh PC, et al.: PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014, 515(7528):568-71.
  • [5]Yadav M, et al.: Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 2014, 515(7528):572-6.
  • [6]Gubin MM, et al.: Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014, 515(7528):577-81.
  • [7]Gallagher DJ, et al.: Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 2010, 28(8):1373-9.
  • [8]Ko YJ, et al.: Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol 2013, 14(8):769-76.
  • [9]Necchi A, et al.: Pazopanib in advanced and platinum-resistant urothelial cancer: an open-label, single group, phase 2 trial. Lancet Oncol 2012, 13(8):810-6.
  • [10]Sweeney CJ, et al.: Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol 2006, 24(21):3451-7.
  • [11]Wolchok JD, et al.: Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013, 369(2):122-33.
  • [12]Topalian SL, et al.: Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014, 32(10):1020-30.
  • [13]Hamid O, et al.: Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013, 369(2):134-44.
  • [14]Speiser DE, et al.: T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion? Nat Rev Immunol 2014, 14(11):768-74.
  • [15]Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011, 144(5):646-74.
  • [16]Lawrence MS, et al.: Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013, 499(7457):214-8.
  • [17]Vogelstein JT, Gray Roncal W, Vogelstein RJ, Priebe CE: Graph classification using signal-subgraphs: applications in statistical connectomics. IEEE Trans Pattern Anal Mach Intell 2013, 35(7):1539-51.
  • [18]van Rooij N, et al.: Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma. J Clin Oncol 2013, 31(32):e439-42.
  • [19]Lundegaard C, Lund O, Nielsen M: Prediction of epitopes using neural network based methods. J Immunol Methods 2011, 374(1–2):26-34.
  • [20]Nielsen M, et al.: Reliable prediction of T-cell epitopes using neural networks with novel sequence representations. Protein Sci 2003, 12(5):1007-17.
  • [21]Peters B, Sette A: Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method. BMC Bioinformatics 2005, 6:132. BioMed Central Full Text
  • [22]Vita R, et al.: The immune epitope database 2.0. Nucleic Acids Res 2010, 38(Database issue):D854-62.
  • [23]Castle JC, et al.: Exploiting the mutanome for tumor vaccination. Cancer Res 2012, 72(5):1081-91.
  • [24]Snyder A, et al.: Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014, 371(23):2189-99.
  • [25]Brahmer JR, et al.: Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012, 366(26):2455-65.
  • [26]Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma. N Engl J Med 2015;372:311-319 doi:10.1056/NEJMoa1411087.
  • [27]Topalian SL, et al.: Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012, 366(26):2443-54.
  • [28]Erdag G, et al.: Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 2012, 72(5):1070-80.
  • [29]Harbst K, et al.: Molecular profiling reveals low- and high-grade forms of primary melanoma. Clin Cancer Res 2012, 18(15):4026-36.
  • [30]Spranger S, et al.: Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 2013, 5(200):200ra116.
  文献评价指标  
  下载次数:6次 浏览次数:4次