Predictive Biomarkers and Targeted Therapies in Immuno-oncology

  • Hartmut KoeppenEmail author
  • Mark L. McCleland
  • Marcin Kowanetz


Cancer immunotherapy (CIT) has transformed our approach in diagnosis and treatment of cancer. However, durable responses or cures are only seen in a minority of patients, illustrating the need for reliable biomarkers that identify patients most likely to receive meaningful clinical benefit. PD-L1 immunohistochemistry (IHC) has been extensively used in clinical development programs for anti-PD-L1/PD-1 targeted therapies. Notably, four independently developed PD-L1 IHC assays have demonstrated clinically meaningful predictive value in several indications and are approved as companion or complementary diagnostics. PD-L1 IHC is by no means a flawless biomarker or diagnostic. Numerous studies have found that a subset of PD-L1 negative patients do in fact derive clinical benefit from CIT therapy, highlighting the need for more precise diagnostic tools. Gene signatures with emphasis on immune-related biology and tumor mutation burden, a surrogate for neoantigen presentation, have both emerged as new promising CIT biomarkers and have demonstrated predictive value in exploratory clinical studies. As of today, neither of these biomarkers has gained approval as a companion or complementary diagnostic or has shown the capacity to accurately capture all patients that could potentially benefit from CIT. It is likely, based on the complexity of the tumor microenvironment, that more than one biomarker will be required to identify patients that benefit from CIT in the future.


Cancer immunotherapy Predictive biomarker Companion diagnostic PD-L1 PD-1 Immunohistochemistry Gene signatures Tumor mutational burden (TMB) SP142 SP263 22c3 28-8 Atezolizumab Pembrolizumab Nivolumab Durvalumab Tumor-infiltrating lymphocytes (TILs) 


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Hartmut Koeppen
    • 1
    Email author
  • Mark L. McCleland
    • 2
  • Marcin Kowanetz
    • 2
  1. 1.Research PathologyGenentechSouth San FranciscoUSA
  2. 2.Department of Oncology Biomarker DevelopmentGenentechSouth San FranciscoUSA

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