Evaluation of PD-L1 Expression in Undifferentiated Pleomorphic Sarcomas, Liposarcomas and Chondrosarcomas.

Yifan Zhang,Panagiotis Tsagkozis,Andri Papakonstantinou,Felix Haglund,Yi Chen,Christina Linder-Stragliotto

doi:10.3390/biom12020292

Yifan Zhang, Panagiotis Tsagkozis + Show 4 more

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https://doi.org/10.3390/biom12020292

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Abstract

Immune checkpoint inhibitors (ICIs) such as PD1/PD-L1 blockers are an established treatment for many solid cancers. There are currently no approved ICIs for sarcomas, but satisfactory results have been seen in some patients with disseminated disease in certain histological types. Most studies on PD-L1 in sarcoma have used small specimens and there are no clear cutoff values for scoring. We investigated PD-L1 immunoreactivity in high-grade chondrosarcomas (CS), abdominal liposarcoma (LS) and undifferentiated pleomorphic sarcomas (UPS). In total, 230 tumors were stained with SP142 and SP263 assays and evaluated by two clinical pathologists. Immunoreactivity in tumor and immune cells was correlated with clinical outcome. Overall, ≥1% PD-L1 immunoreactivity in tumor cells was found in 11 CS, 26 LS and 59 UPS (SP142 assay) and in 10 CS, 26 LS and 77 UPS (SP263 assay). Most tumors exhibited ≤10% PD-L1 immunoreactivity, but a subset across all three subtypes had >50%. Kaplan–Meier survival analysis showed no significant difference in metastasis-free or overall survival in relation to PD-L1 immunoreactivity in tumor or immune cells for any subtype. As there is a lack of clinical data regarding PD-L1/PD-1 status and therapy response, it is not currently possible to establish clear cutoff values. Patients with high (>50%) PD-L1 immunoreactivity in tumor cells (TC) with the SP263 assay would be a logical group to investigate for potentially beneficial PD1/PD-L1-targeted treatment.

Highlights

The complex network of interactions present in the tumor microenvironment has in recent years risen, as the new frontier of targeted cancer therapies for a number of malignant tumors, with the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway as the currently most widely utilized target
We aimed to categorically investigate and quantify PD-L1 immunoreactivity in three major sarcoma subtypes; chondrosarcoma (CS), liposarcoma (LS) and undifferentiated pleomorphic sarcoma (UPS), using the SP142 and SP263 assays, which are two of the most used in vitro diagnostic regulation (IVDR)-approved PD-L1 immunohistochemistry assays used in clinical settings
We found no significant association between PD-L1 immunoreactivity and overall survival

Summary

Introduction

The complex network of interactions present in the tumor microenvironment has in recent years risen, as the new frontier of targeted cancer therapies for a number of malignant tumors, with the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway as the currently most widely utilized target. PD-L1 is a type 1 transmembrane protein, and a ligand to PD-1, a receptor found on T, B and myeloid cells. The binding of PD-1 and PD-L1 suppresses the adaptive immune system by interactions with phosphatases (SHP-1 or -2) via ITSM Switch Motif [1,2]. Tumor cells utilize this mechanism to escape the immune system, which in turn, by inhibiting this bond, may properly identify and attack tumor cells. PD-L1 immunoreactivity is part of routine workup in many solid cancers, but is not yet established in sarcomas.

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