Development and clinical applications of cancer immunotherapy against PD-1 signaling pathway

Table 3 Predictive biomarkers for treatment efficacy of PD-1/PD-L1 targeting agents

Drug	Sample	Marker	Result	Reference
Pembrolizumab	NSCLC	PD-L1*	↑: longer OS & PFS	Herbst et al., 2016; Reck et al., 2016; Mok et al., 2019
Pembrolizumab	Metastatic colon cancer	MMR*	Deficiency: ORR = 40%, DCR = 90%	Le et al., 2016
Pembrolizumab	11 cancer types	MMR*	Deficiency: ORR = 53%, DCR = 77%	Le et al., 2017
Nivolumab	NSCLC	TMB	↑: longer PFS	Carbone et al., 2017
Nivolumab+Ipilimumab	NSCLC	TMB	↑: longer OS & PFS	Hellmann et al., 2018
Nivolumab	melanoma	ALC	≥ 1000u/L: ↑ prognosis	Nakamura et al. 2016
Nivolumab	melanoma	ANC	< 4000u/L: ↑ prognosis	Nakamura et al. 2016
Ipilimumab	melanoma	NLR + LDH	NLR > 2.2 & ↑LDH: ↓ RR	Bagley et al., 2017
PD-1 targeted therapy	NSCLC	Ki67	↑: positive outcomes	Kamphorst et al., 2017
Pembrolizumab	melanoma	TCR repertoire	↓ diversity: positive clonal responses	Tumeh, et al., 2014
Nivolumab	Metastatic melanoma	PD-L1 + GZMA + HLA-A	↑: better clinical outcomes	Hiroyuki et al., 2016
Nivolumab	Metastatic melanoma	TCR repertoire	↓ diversity: ↑ responses	Hiroyuki et al., 2016; Sabrina et al., 2018
PD-1 targeted therapy	melanoma	Ruminococcaceae family	↑ alpha diversity & relative abundance: ↑ responses	Gopalakrishnan et al., 2018
PD-1 targeted therapy	Lung & kidney cancers	Akkermansia muciniphila	↑ relative abundance: ↑ responses	Routy et al., 2018

* PD-L1 and MMR are clinically applicable biomarkers
NSCLC Non-small-cell lung carcinoma, OS Overall survival, PFS Progression free survival, ORR Overall response rate, DCR Disease control rate, TMB Tumor mutation burden, ALC Absolute lymphocyte count, NLR Neutrophil-to-lymphocyte ratio, LDH Lactate dehydrogenase, RR Response rate, TCR T-cell receptor

ISSN: 1423-0127