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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (1) : 32-44
Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy
Min Zhang, Jingwen Yang, Wenjing Hua, Zhong Li, Zenghui Xu(), Qijun Qian()
ShangHai Cell Therapy Group Co., Ltd., Shanghai 201805, China
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Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.

Keywords immune checkpoint      companion diagnosis      PD-L1      tumor mutation burden      immune score     
Corresponding Authors: Zenghui Xu,Qijun Qian   
Just Accepted Date: 10 January 2019   Online First Date: 25 January 2019    Issue Date: 12 March 2019
 Cite this article:   
Min Zhang,Jingwen Yang,Wenjing Hua, et al. Monitoring checkpoint inhibitors: predictive biomarkers in immunotherapy[J]. Front. Med., 2019, 13(1): 32-44.
Fig.1  Potential biomarkers for checkpoint inhibitors in category. Tumor-specific atlas (left) includes the expression of PD-L1, neoantigen, and MSI. Tumor microenvironment (right) includes tumor-infiltrating lymphocytes and immune score (not shown in the figure). Biomarkers in the serum (below) contains molecules CRP, LDH, and IL-6 and lymphocytes in the epithelial serum.
Target Drug trade name
(generic name)
Device trade name PMA Intended use
PD-L1 IHC 22C3 pharmDx P150013/S011 Companion diagnostic devices
?Non-small cell lung cancer (NSCLC)
??The specimen should be considered to exhibit PD-L1 expression if TPS≥1% ???and high PD-L1 expression if TPS≥50%
?Gastric or gastresophageal junction (GEJ) adenocarcinoma
??The specimen should be considered to exhibit PD-L1 expression if CPS≥1
Cervical cancer
??The specimen should be considered to exhibit PD-L1 expression if CPS≥1
Urothelial carcinoma
??The specimen should be considered to exhibit PD-L1 expression if CPS≥10
P150013/S006 Companion diagnostic devices
?Non-small cell lung cancer (NSCLC)
??The specimen should be considered to exhibit PD-L1 expression if TPS≥1 ???and high PD-L1 expression if TPS≥50%
P150013/S001 Companion diagnostic devices
?Non-small cell lung cancer (NSCLC)
??The specimen should be considered PD-L1 positive if TPS≥50% of the ???viable tumor cells exhibit membrane staining at any intensity
PD-L1 28-8 pharmDx P150027/P150027 Complementary diagnostic devices
?Non-small cell lung cancer (NSCLC)
??A minimum of 100 viable tumor cells must be present for the specimen to be ???considered adequate for PD-L1 evaluation
??Specimen is considered PD-L1 positive if≥1% of melanoma cells exhibit ???circumferential and/or partial linear plasma membrane PD-L1 staining of ???tumor cells at any intensity
PD-L1 (SP142) P16002/S006 Companion diagnostic devices
?Urothelial carcinoma
??PD-L1 expression≥5% IC is indicated as an aid in identifying urothelial ???carcinoma patients
?Non-small cell lung cancer (NSCLC)
??PD-L1 expression≥50% TC or≥10% IC may be associated with enhanced ???overall survival
PD-L1 SP263 P160046 Complementary diagnostic devices
?Advanced or metastatic urothelial carcinoma
??PD-L1 status is considered high if any of the following are met: (1)≥25% of ???tumor cells exhibit membrane staining; (2) ICP>1% and IC+≥25%;(3) ICP???= 1% and IC+ = 100%
Tab.1  List of diagnostic devices approved by FDA
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