TY - JOUR
T1 - Biomarkers of immunotherapy in urothelial and renal cell carcinoma
T2 - PD-L1, tumor mutational burden, and beyond
AU - Zhu, Jason
AU - Armstrong, Andrew J.
AU - Friedlander, Terence W.
AU - Kim, Won
AU - Pal, Sumanta K.
AU - George, Daniel J.
AU - Zhang, Tian
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2018/1/25
Y1 - 2018/1/25
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Immune checkpoint inhibition
KW - PD-L1
KW - Renal cell carcinoma
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85041001162&partnerID=8YFLogxK
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U2 - 10.1186/s40425-018-0314-1
DO - 10.1186/s40425-018-0314-1
M3 - Review article
C2 - 29368638
AN - SCOPUS:85041001162
SN - 2051-1426
VL - 6
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 1
M1 - 4
ER -