Four immunohistochemical assays to measure the PD-L1 expression in malignant pleural mesothelioma

Abstract

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway are expected to be a novel therapy for combating future increases in numbers of malignant pleural mesothelioma (MPM) patients. However, the PD-L1 expression, which is a predictor of the response to ICIs, is unclear in MPM. We studied the PD-L1 expression using four immunohistochemical assays (SP142, SP263, 28-8 and 22C3) in 32 MPM patients. The PD-L1 expression in tumor cells and immune cells was evaluated to clarify the rate of PD-L1 expression and the concordance among the four assays in MPM. The positivity rate of PD-L1 expression was 53.1% for SP142, 28.1% for SP263, 53.1% for 28-8, and 56.3% for 22C3. Nine cases were positive and 10 were negative for all assays. Discordance among the four assays was found in 13 cases. The concordance rates between SP142 and 22C3 and between 28-8 and 22C3 were the highest (84.4%). The concordance rates between SP263 and the other three assays were low (71.9% to 75.0%). The PD-L1 expression in MPM was almost equivalent for three of the assays. Given the cut-off values set in our study, these findings suggested that these assays, except for SP263, can be used for accurate PD-L1 immunostaining in MPM.

Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma

“…Our results showed that PD-L1 expression does not appear to be significantly associated with survival despite a trend toward a poorer prognosis with PD-L1 expression in ≥50% on tumor cells. The absence of a significant association with survival is in agreement with two recent studies, in which a specific antibody (SP142) (38) and four different antibodies were employed (17). This finding was observed even when we compared survival with PD-L1 expression on TILs, and with the combined expression of tumor cells and TILs.…”

“…Of note, we reported an association between PD-L1 positivity and histotype. Furthermore, some studies have found lower PD-L1 expression in epithelioid subtype compared with other subtypes (15)(16)(17)(18). PD-L1 on tumor cells was not always expressed simultaneously with PD-L1 on TILs as already reported (15,16,21) and in concordance with the findings in other tumor types (33).…”

“…Immune checkpoint inhibitors (ICIs) have already shown promising results in other tumors (13), and are also under investigation in MM in which the expression of PD-L1 has been detected, regardless of the predictive value in this neoplasia (3,14). ≥1% PD-L1 expression is reported with different percentages in patients with MM (15)(16)(17)(18)(19)(20)(21), with higher positivity rates in non-epithelioid subtypes (18,19). Given the interaction between immune infiltrate and neoplastic cells, the characterization of TME could be of great value not only to understand the immune response, but also to determine its possible prognostic value.…”

Programmed death–ligand 1 expression on direct Pap‐stained cytology smears from non–small cell lung cancer: Comparison with cell blocks and surgical resection specimens

“…Quantification of PD‐L1 expression in patients with advanced NSCLC is useful for predicting the response to immunotherapy with checkpoint inhibitors that disrupt the PD‐1/PD‐L1 interaction . Two commercially available PD‐L1 IHC assays, the PD‐L1 IHC 22C3 pharmDx and the Ventana PD‐L1 SP263 assays, have been shown to be highly concordant in quantifying PD‐L1 expression regardless of the TPS cutoff levels or sample type (surgical resections/biopsies vs cytological specimens) …”

Immune checkpoints in thymic epithelial tumors: challenges and opportunities

“…Data from the Cancer Genome Atlas and Foundation Medicine indicated a low tumor mutation burden in thymomas and thymic carcinomas; only 6% of carcinoma cases had >10 mutations/Mb and 3% had >20 mutations/Mb (Figure 2) [13,15]. [30] TMA, clone 5H1 (intensity high) 65 44 (68%) 4 3 (75%) Arbour et al [31] Slides, clone E1L3 (25% of tumor cells cut off) 12 11 (94%) 11 4 (34%) Yokohama et al [32,33] Slides, EPR1161 (H-score, 20% of tumor cells cut off) 82 44 (54%) 25 20 (80%) Weissferdt [34] Slides, clone E1L3 (5% of tumor cells cut off) 74 47 (64%) 26 14 (54%) Markevski et al [28] Slides, clone SP142 (1% of tumor cells cut off) 38 35 (92%) 8 4 (50%) Wei et al [35] TMA, clone E1L3 (% of cells and intensity) 100 100 (100%: 36% low, 64 high) 69 69 (100%: 64% low, 36% high) Guleria et al [36] TMA, clone SP263 (1-25% of tumor cells cut off) 84 69 (82%) Suster et al [37] TMA, clone SP142 (1-50% of tumour cells cut off) 21 (lymphoepithelioma like histology) 15 (71%: 67% high, 33% low) Tiseo et al [38] TMA, clone E1L3 (H-score, 1% of tumor cells cut off) 87 16 (20%) 25 13 (52%) Bagir et al [39] Slides, clone AM26531AF-N (intensity) 37 21 (57%) 6 4 (67%) Sakane et al [40] Slides…”