Introduction

             

Biomarkers have multiple applications in oncology, including risk assessment, screening, differential diagnosis, determination of prognosis, prediction of response to treatment and monitoring of disease progression.

The programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway is an important checkpoint used by tumour cells to inhibit anti-tumour immune responses.1 PD-L1 expression reduces T-cell activation by binding to PD-1, which reduces cytokine production and T-cell proliferation.2

Blockage of PD-L1 can overcome this immune checkpoint, resulting in prolonged T-cell activation and tumour rejection.1 The use of anti-PD-1/PD-L1 antibodies in the treatment of cancers, including bladder cancer and non-small cell lung cancer (NSCLC), is associated with clinical benefit.3, 4 Further, higher response rates to anti-PD-1/PD-L1 therapies have been observed in patients whose tumours are characterised by increased PD-L1 expression, compared with tumours containing low PD-L1 expression.5-9

Therefore, it is important to determine PD-L1 expression in patient tumour samples before considering therapeutic interventions, in order to make effective treatment decisions.

 

 

Mechanism of action of
anti-PD-L1 therapy

PD-L1 expression leads to
immune cell evasion

Anti-PD-1/PD-L1 reverses
immune supperession

 

Figure adapted from Peters, et al. 201910
PD-1, programmed cell death-1; PD-L1, programmed cell death ligand-1

The role of PD-L1 testing for immunotherapy

 

Professor Patrick Pauwels (University of Antwerp, Belgium) discusses the role of PD-L1 testing for immunotherapy.

Results from PD-L1 testing can complement other factors that may influence treatment decisions in oncology, such as patient age, performance status and tumour stage.11-13

Factors influencing treatment decisions in oncology11-13

ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; PD-L1, programmed cell death ligand-1; ROS-1, ROS proto-oncogene 1

 

 

  1. Wu Y, Chen W, Xu ZP, et al. PD-L1 distribution and perspective for cancer immunotherapy-blockade, knockdown, or inhibition. Front Immunol 2019;10:2022
  2. Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000;192:1027–1034
  3. Stenehjem DD, Tran D, Nkrumah MA, et al. PD1/PDL1 inhibitors for the treatment of advanced urothelial bladder cancer. Onco Targets Ther 2018;11:5973–5989
  4. Meyers DE, Bryan PM, Banerji S, et al. Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer. Curr Oncol 2018;25:e324–e334
  5. Massard C, Gordon MS, Sharma S, et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 2016;34:3119–3125
  6. Balar AV, Castellano D, O'Donnell PH, et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017;18:1483–1492
  7. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 2016;387:1909–1920
  1. Aguilar EJ, Ricciuti B, Gainor JF, et al. Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol 2019;30:1653–1659
  2. Passiglia F, Bronte G, Bazan V, et al. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis. Oncotarget 2016;7:19738–19747
  3. Peters S, Cho BC, Reinmuth N, et al. Abstract CT074: Tumor mutational burden (TMB) as a biomarker of survival in metastatic non-small cell lung cancer (mNSCLC): blood and tissue TMB analysis from MYSTIC, a phase III study of first-line durvalumab ± tremelimumab vs chemotherapy. AACR Annual Meeting 2019; Atlanta, GA, USA 2019. CT074
  4. Powles T, Walker J, Andrew Williams J, et al. The evolving role of PD-L1 testing in patients with metastatic urothelial carcinoma. Cancer Treat Rev 2020;82:101925
  5. Tabchi S, Kassouf E, Florescu M, et al. Factors influencing treatment selection and survival in advanced lung cancer. Curr Oncol 2017;24:e115–e122
  6. Pennell NA, Arcila ME, Gandara DR, et al. Biomarker testing for patients with advanced non-small cell lung cancer: real-world issues and tough choices. Am Soc Clin Oncol Educ Book 2019;39:531–542