Table 4.

Immunohistochemical methods for evaluating tumor PD-L1 expression

Laboratory	JHU	Bristol-Myers Squibb						Merck			Roche/Genentech
mAb clone	5H1	28–8						22C3			SP142
Automated	No	Yes						Yes			Yes
Staining location scored	Membrano us	Membranous						Membranous			Membranous
Cell type scored	Tumor	Tumor						Tumor and/or infiltrating immune cells			Infiltrating immune cells
"positive" cutoff^a	> 5%	>5%						>1%			≥ 1% and < 5% (“IHC 1”); ≥ 5% and < 10% (“IHC 2”); ≥ 10% (“IHC 3”)
Tumor type	Melanoma, NSCLC, Renal, Colorectal, Prostate	Melanoma	Melanoma	Melanoma	NSCLC	NSCLC	KCC	HNSCC	Melanoma	NSCLC^b	Bladder	Melanoma	NSCLC	Solid Tumors
PD-L1 positive patients/total patients (%)	25/42(60)	12/44 (27)	17/38 (45)	74/210 (35)	9/15 (60)	33/68 (49)	29/107 (27)	81/104 (78)	89/125 (71)	159/194 (82)	55/205 (27)^c	15/30 (50)^d	48/184 (26)^e	181/732 (25)^d
Reference #	3	14	67	6	26	23	32	53	68	32	36	70	18	18

PD-L1 expression in formalin-fixed, paraffin embedded (FFPE) tumor specimens was evaluated using distinct immunohistochemical assays and scoring methods. Some references report results from different cut-offs for positive scoring in the same cohorts. Final methods and cut-off values are likely to be determined after additional clinical follow-up and analysis of ongoing studies.

^(a)

Positive cutoff, definition of PD-L1 positive specimen according to threshold percent of cells staining with PD-L1 specific mAb.

^(b)

Updated scoring system for NSCLC defines a PD-L1+ specimen as having ≥1% tumor cells expressing cell surface PD-L1, and subdivides “strong” positives (≥50% staining) vs. “weak” positives (<50% staining).²⁸

^(c)

PD-L1+ defined as IHC 2 and IHC 3.

^(d)

PD-L1 + defined as ≥5% infiltrating cells or tumor cells expressing PD-L1.

^(e)

PD-L1+ defined as “tumors with infiltrating immune cells that stain for PD-L1 using Genentech/Roche Ex IHC”.

JHU, Johns Hopkins University.