PD-L1 is a potential predictive biomarker for cancers that utilise this pathway to inhibit the immune response
Tumour cells and tumour-infiltrating immune cells both express PD-L11,2
PD-L1 expression detected in immunohistochemistry staining of lung cancer tumour3
PD-L1 on tumour cells may lead to the inhibition of activated T cells1
Tumour-infiltrating immune cell
PD-L1 on tumour-infiltrating immune cells may also inhibit T cell activation and function.1,4
PD-L1 expression on tumour-infiltrating immune cells
With their potential ability to inhibit T cell function when expressing PD-L1, tumour-infiltrating immune cells are an emerging focus of cancer immunotherapy research.1,4 Different immune cells have been shown to express PD-L1.3
PD-L1 expression on macrophages detected in immunofluorescence staining of lung cancer tumour3
Arrows indicate macrophages (green; CD163) that express PD-L1 (red). Cell nuclei are stained in blue.
Arrows indicate macrophages (green; CD68) that expressPD-L1 (red). Cell nuclei are stained in blue.
Understanding PD-L1 expression on tumour cells and tumour-infiltrating immune cells may impact personalised cancer immunotherapy research1,5
As a primary immunosuppressive driver, high expression levels of PD-L1 may be an important facilitator for tumour growth and metastasis. PD-L1 has been detected in up to 50% of human cancers, making the PD-L1 pathway a focus of cancer research.1,4-6
The presence of tumour-infiltrating immune cells has also been reported in many of these cancer types.7-21 Because these immune cells can also express PD-L1, the assessment of PD-L1 on tumour cells and tumour-infiltrating immune cells may be an important consideration for cancer immunotherapy research.
|CANCER TYPE||PERCENTAGE POSITIVE
FOR PD-L1 EXPRESSION1*
|PRESENCE OF TUMOUR-
|Non-small cell lung cancer||35%–95%||9|
|Renal cell carcinoma||15%–24%||20|
- *Table modified according to Chen DS, et al, a review of current literature on PD-L1 expression. 1
- † Percentage of PD-L1 expression is unknown.
- ‡ Includes peripheral T cell lymphomas, diffuse large cell lymphoma, or small lymphocytic lymphoma.
PD-L1 is a potential predictive biomarker under investigation
Based on clinical studies, PD-L1 expression has been associated with response to PD-L1/PD-1 inhibition, suggesting that cancers with high PD-L1 expression are more likely to respond to immunotherapies that target the PD-L1 pathway.1,6
Roche is actively investigating PD-L1 as a potential predictive biomarker in cancer research and is committed to pursuing the potential of personalised cancer immunotherapy for cancer patients.
- Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy—inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18:6580-6587. PMID: 23087408
- Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res.2013;19:1021-1034. PMID: 24048329
- Data on file. Roche, Inc.
- Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. PMID: 18173375
- Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
- Quezada SA, Peggs KS. Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune response against cancer. Br J Cancer.2013;108:1560-1565. PMID: 23511566
- Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-264. PMID: 22437870
- Taylor RC, Patel A, Panageas KS, Busam KJ, Brady MS. Tumour-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. J Clin Oncol. 2007;25:869-875. PMID: 17327608
- Hiraoka K, Miyamoto M, Cho Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer. 2006;94:275-280. PMID: 16421594
- Hsu MM, Hsu HC, Lui LT. Local immune reaction in nasopharyngeal carcinoma, with special reference to its prognostic evaluation. Head Neck. 1989;11:505-510. PMID: 2479615
- Berghoff AS, Kiesel B, Widhalm G, et al. Programmed death ligand 1 expression and tumour-infiltrating lymphocytes in glioblastoma. Neuro Oncol. 2014. doi:10.1093/neuonc/nou307. PMID: 25355681
- Matsuda S, Yamane T, Hamaji M. CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues. Jpn J Clin Oncol. 1998;28:97-103. PMID: 9544823
- Gao Q, Wang XV, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumour aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15:971-979. PMID: 19188168
- Sharma P, Shen Y, Wen S, et al. CD8 tumour-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007;104:3967-3972. PMID: 17360461
- Noonan K, Matsui W, Serafini P, et al. Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res. 2005;65:2026-2034. PMID: 15753403
- Zhang l, Conejo-Garcia JR, Katsaros D, et al. lntratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med.2003;348:203-213. PMID: 12529460
- Okita Y, Tanaka H, Ohira M, et al. Role of tumour-infiltrating CD11b+ antigen-presenting cells in the progression of gastric cancer. J Surg Res. 2014;186:192-200. PMID: 24120241
- Schumacher K, Haensch W, Röefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res. 2001;61:3932-3936. PMID: 11358808
- Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumour microenvironment of patients with pancreas or breast adenocarcinoma. J lmmunol. 2002;169:2756-2761. PMID: 12193750
- Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumour-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007;13:1757-1761. PMID: 17363529
- Chen BJ, Chapuy B, Ouyang J, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19:3462-3473. PMID: 23674495
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