PD-L1 expression in the microenvironment and the response to checkpoint inhibitors in head and neck squamous cell carcinoma

Figures & data

Table 1. Results about prognostic value of PD-L1 expression in HNSCC pre-clinical studies

Reference	Year	Tumor types	Cells analyzed	Clone of antibody	Cutoff	Incidence of PD-L1	Correlation with OS	Correlation with HPV status
Strome et al.	2003	HNSCC	TC	mAb 5H1	>0%	66	NE	NE
Lyford-Pike et al.	2006	HNSCC HPV+	TC	mAb 5H1	>5%	70	NE	+
Zhang et al.	2008	NPC	U	U	U	68	-	NE
Hsu et al.	2010	NPC	TC and IC	MIH1,; eBioscience,		100	NE	NE
Cho et al.	2011	OSCC	TC	ab82059, abcam,		87	-	-
Badoual et al.	2013	HNSCC		Goat anti-PDL-1 (R&D)	>20%	52	-	NE
Ukpo et al.	2013	OPSCC HPV+	TC	clone A3	>5%	49	-	-
Malm et al.	2015	HNSCC HPV-	TC and IC	5H1, isotype mouse IgG1	>5%	78	NE	NE
Hong et al.	2016	OPSCC	TC	E13LN	>1%	70	+	+
Kim et al.	2016	OPSCC	TC	mAb 5H1	≥20%	68	-	-
Solomon et al.	2016	OPSCC HPV+	TC	SP142; Spring Bioscience	≥1%	47	-	NE
			IC		>5%	18	-	NE
Oguejiofor et al.	2017	OPSCC	TC and IC	rabbit monoclonal, Cell signaling	≥5%	21	NE	+

HPV, human papilloma virus; IC, immune cells; NE, not evaluated; NPC, nasopharyngeal carcinoma; OSCC, oral squamous cell carcinoma; OPSCC, oropharyngeal squamous cell carcinoma; TC, tumor cells; U, unspecified

Table 2. Results about prognostic value of PD-L1 expression in HNSCC clinical trials

Reference	Year	Protocol	Cells analyzed	Clone of antibody	Cutoff	of PD-L1+	Correlation with anti-PD1 response
Ferris et al. NEJM	2017	Checkmate 141	TC	clone 28–8, Epitomics	≥1%	149	+
					≥5%	97	+
					≥10%	77	-
Ferris et al. OO	2016	Checkmate 141	TC	clone 28–8, Epitomics	≥1%	55	+
					≥5%	34	+
					≥10%	27	-
Seiwert et al.	2016	KEYNOTE-012	TC and IC	22C3, Merck	≥1	100%	NEV
Chow et al.	2016	KEYNOTE-012	TC	22C3, Merck	≥1%	67%	-
			TC and IC		≥1	81%	+
Bauml et al.	2017	KEYNOTE-055	TC and IC	22C3, Merck	≥1	84%	+
					≥50	29%	+
Cohen et al.	2018	KEYNOTE-040	TC and IC	22C3, Merck	≥1	78%	+
Burtness et al.	2018	KEYNOTE-048	TC and IC	22C3, Merck	≥1	85%	+
					≥20	40%	+

IC, immune cells; TC, tumor cells

Table 3. Studies comparing different PD-L1 IHC assays

	# and types of tested tumors	SP142	SP263	28–8	22C3	E1L3N	Ref
Hirsch et al.	39 NSCLC	-	+	+	+	NE	26
Karim et al.	29 NSCLC	+	NE	+	+		27
Scognamiglio et Chen	96 HNSCC	+	+++	NE	NE	+	21
Rimm et al.	90 NSCLC	-	NE	+	+	NE	28

Abbreviations: #, number; HNSCC, head and neck squamous cell carcinoma; NE, not evaluated; NSCLC, non–small-cell lung cancer.

SP142 (Spring Bioscience), SP263 (Ventana), 28–8 (Dako), 22C3 (Dako) and E1L3N (Cell Signaling)

Figure 1. PD-L1 staining (E1L3N, Cell signaling technology) in head and neck carcinoma sample shows a weak staining of the tumor component (t) contrasting with a strong staining of the immune component (i) located in the stroma. Pathologists have scored this case 15% by tumor proportion score (TPS) and 40 by combined positive score (CPS)

Table 4. Response to the PD-1/PD-L1 inhibitors according to PD-L1 expression in HNSCC clinical trials

Reference	ORR for all the patients included with nivo/pembro		For CPS			For TS
% of patients with CPS≥1%	Response (%) of patients with CPS≥1%	Response (%) of patients with CPS<1%	% of patients with TS≥1% in group Nivo/pembro		Response (%) of patients with TS≥1%	Response (%) of patients with TS<1%
Pembrolizumab
Keynote 012 (Seiwert)	18 (8/45)				100%		18 (8/45)	NEV
Keynote 012 (Chow)	18 (24/132)	81 (107/132)	21 (23/107)	4 (1/25)	67 (89/132)		19 (17/89)	16 (7/43)
Keynote 055 (Bauml)	17 (28/166)	84 (140/166)	18 (25/140)	12 (3/26)
Keynote 040 (Cohen)	14 (36/247)	78(387/495)	17 (34/196)	4 (2/50)
Keynote 048 (Burtness)	23(31/133) for CPS≥20 19 (49/257) for CPS≥1	85 (754/882)	19(49/257)	NR
Nivolumab
Checkmate 141 NEJM	13 (32/240)	NR	NR	NR	55(88/161)		17 (15/88)	12.3 (9/73)
Checkmate 141 OO	13 (32/240)

CPS, combined positive score; NEJM, New England Journal of Medicine; Nivo, nivolumab; Pembro, pembrolizumab; TPS, tumor proportion score; NR, not reported; OO, oral oncology.

Table

CPS	combined positive score
EMA	European Medicine Agency
FDA	Food and Drug Administration
HNSCC	head and neck squamous cell carcinoma
NSCLC	non–small cell lung cancer
OS	overall survival
PD-1	programmed death-1
PD-L1	programmed death ligand 1
PFS	progression-free survival
R/M	recurrent/metastatic
TAM	tumor-associated macrophage
TIL	tumor-infiltrating lymphocyte
TPS	tumor proportion score