Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond

Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.

Journal for immunotherapy of cancer. 2018 Jan 25*** epublish ***

Jason Zhu, Andrew J Armstrong, Terence W Friedlander, Won Kim, Sumanta K Pal, Daniel J George, Tian Zhang

Duke University Health System, Durham, NC, USA., Duke Cancer Institute, DUMC 103861, Durham, NC, 27710, USA., University of California San Francisco, San Francisco, CA, USA., City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA., Duke Cancer Institute, DUMC 103861, Durham, NC, 27710, USA. .