Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus

Abstract

Poorly differentiated non-keratinizing squamous cell carcinoma of the thymus, also known as lymphoepithelioma-like carcinoma, is a rare primary malignant neoplasm of thymic origin. The mainstay of treatment for these tumors is surgical and they tend to respond poorly to chemotherapy. The checkpoint programmed cell death ligand-1 protein (PD-L1) bound to its receptor (PD-1) has been demonstrated to be an important therapeutic target for many different tumors. Expression of PD-L1/PD-1 in lymphoepithelioma-like carcinoma of the thymus may indicate that these tumors are potential targets for inhibitor therapy. Twenty-one cases of lymphoepithelioma-like carcinoma of the thymus were collected and reviewed. Tissue microarrays were created using triplicate 2 mm cores for each case. PD-L1/PD-1 staining pattern (neoplastic cells versus tumor infiltrating lymphocytes) was documented for each case. Out of 21 cases, 15 (71.4%) showed various degrees of membranous PD-L1 staining. Of the positive cases, 48% showed high expression of PD-L1 (>50% of tumor cells) and 24% showed low expression (<50%). PD-1 staining showed focal positivity in 12/20 (60%) cases among tumor infiltrating lymphocytes. PD-L1/PD-1 inhibitor therapy has been applied successfully in other solid malignant tumors with high expression of PD-L1/PD-1. The high level of PD-L1 expression in our cases indicates that PD-L1 may play a role in the pathogenesis of these tumors and that PD-L1/PD-1 blockade may be a viable therapeutic option for patients with lymphoepithelioma-like carcinoma of the thymus who have failed other first-line therapies.

A multicenter analysis of genomic profiles and PD-L1 expression of primary lymphoepithelioma-like carcinoma of the lung

“…Consistent with our findings, investigations on patients with lymphoepithelioma-like carcinoma of the thymus have also revealed the absence of actionable genes as well as the detection of various degrees of membranous PD-L1 staining in their cohort (total: 71.4%, 15/21; high expression (>50% of tumor cells): 48%; low expression (<50% of tumor cells): 25%) [51,52]. Moreover, they have observed that the patients with PD-L1 expression contained abundant lymphocytes in the stroma, despite the lack of EBV positivity [52]. In contrast to their report, we did not find a correlation between the PD-L1 expression and extent of lymphocytic infiltration in our cohort (Tables 2 and 3).…”

Checkpoint Inhibition in the Treatment of Unresectable, Advanced Lymphoepithelioma-like Hepatocellular Carcinoma

“…evidence of elevated expression in LELCs, as in our patient, which may underlie potential ICI effectiveness as in other specific tumor subtypes. 17 In addition to the above histologic findings that could suggest plausible benefit from ICIs in LEL-HCC, genomic comparisons between LEL-HCC and HCC have revealed mutational differences that suggest LEL-HCC may be more immunogenic and therefore potentially more susceptible to ICIs. Whole exome sequencing comparisons between conventional HCC and LEL-HCC have identified decreased overall nucleotide variants in specific genes of the Wnt/β-catenin and Notch signaling pathways as well as focal amplification of chromosome 11q13.3 in LEL-HCC.…”

“…Likewise, although PD-L1 tumor expression has not been predictive of benefit of ICIs in HCC, there is evidence of elevated expression in LELCs, as in our patient, which may underlie potential ICI effectiveness as in other specific tumor subtypes. 17 …”

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…”

“…[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]; overall, expression of PD-L1 is common in thymomas and thymic carcinomas, and is usually high and intense. In the micro-environment, a large Inhibition of autoimmune regulator leads to release of autoreactive lymphocytes and autoimmune disorders.…”