Abstract
We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher’s exact and Mann Whitney test were used to establish significance (P <0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all atypical lipomatous tumous/well-differentiated lipoasarcomas, myxoid liposarcomas, synovial sarcomas, pleomorphic liposarcomas, and Ewing sarcomas. PD-L1 IHC was concordant in 81% (38 of 47) of matched/paired samples. PD-L1 IHC was discordant in 19% (9 of 47 matched/paired samples), displaying differences in the proportion of cells expressing PD-L1 amongst paired samples with the percentage of PD-L1-positive cells increasing in the metastatic/recurrent site compared to the primary in 6 of 9 cases (67%). Significant correlation between PD-L1 expression and the degree of TILs was exclusively identified in the general cohort of leiomyosarcomas, but not in other sarcoma subtypes or in metastatic/recurrent samples. We conclude that the prevalence of PD-L1 expression in selected sarcomas is variable and likely to be clone dependent. Importantly, we demonstrated that PD-L1 can objectively increase in a small proportion of metastases/recurrent sarcomas, offering the potential of treatment benefit to immune checkpoint inhibitors in this metastatic setting.
Highlights
The PD-1/PD-L1 axis (Programmed death 1 or CD274/ programmed death-ligand 1) plays a crucial role in immune surveillance
We conclude that the frequency of PD-L1 expression in sarcomas is limited to some sarcoma subtypes and that variable selection of clones and cut-offs contributes to the marked discrepancy across different series
We focused on the SP263 companion kit as this selectively identifies patient’s eligibility to anti-PD-1 and/ PD-L1 inhibitors in lung and urothelial carcinoma
Summary
The PD-1/PD-L1 axis (Programmed death 1 or CD274/ programmed death-ligand 1) plays a crucial role in immune surveillance. The frequency of PD-L1 expression in sarcomas reported in the literature is highly variable with incidences ranging from 0% to 65%[5, 7,8,9,10,11,12,13,14,15,16,17,18,19] In their analysis, some of these series have combined statistical analysis of the two molecularly characteristic groups of sarcomas, that is those associated with recurrent specific genetic events (e.g. translocations or amplification) known to drive tumorogenesis (e.g. t(X;18)(p11.2; q11.2) in synovial sarcoma) and sarcomas with complex karyotype (e.g. myxofibrosarcoma), which lack detectable recurrent gene alterations, as a single entity [20,21,22,23]. Such distinction is fundamental as sarcomas across the different groups and within the same group show distinct clinical behaviour
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