PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes

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 pairedsamples 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.

Resistance to Immune Checkpoint Blockade in Uterine Leiomyosarcoma: What Can We Learn from Other Cancer Types?

“…For instance, abundant expression of programmed cell death-ligand 1 (PD-L1), which has been correlated with immune response and is currently used as a biomarker for ICB therapy in other tumor types, has been observed on tumor cells and tumor-associated immune cells in up to 70% of uLMSs [ 8 , 11 , 12 , 13 ]. Additionally, a substantial fraction of uLMSs show elevated levels of tumor-infiltrating lymphocytes (TILs), widely recognized as a predictive biomarker for response to ICB [ 12 , 13 , 14 ]. Finally, uLMSs have a substantial tumor mutational burden, a genomic biomarker that predicts a favorable response to ICB [ 8 , 15 ].…”