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Evaluation of PD-L1 Expression in Undifferentiated Pleomorphic Sarcomas, Liposarcomas and Chondrosarcomas
Yifan Zhang1,2, Yi Chen2, Andri Papakonstantinou2,3
1Department of Pathology and Cancer Diagnostics, Radiumhemmet, Karolinska University Hospital Solna, 171 64 Solna, Sweden.
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.
Insights
Immune checkpoint inhibitors (ICIs) show promise in sarcomas. This study found no survival difference based on PD-L1 levels, but high PD-L1 expression in tumor cells may warrant further investigation for ICI therapy.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune checkpoint inhibitors (ICIs) like PD1/PD-L1 blockers are effective in various solid cancers.
- Currently, no ICIs are approved for sarcomas, despite some positive responses in patients with disseminated disease.
- Limited data exists on PD-L1 expression in sarcomas, with no established scoring cutoffs.
Purpose of the Study:
- To investigate PD-L1 immunoreactivity in high-grade chondrosarcomas (CS), abdominal liposarcomas (LS), and undifferentiated pleomorphic sarcomas (UPS).
- To correlate PD-L1 expression with clinical outcomes, including metastasis-free and overall survival.
- To evaluate the potential for PD-L1/PD-1 targeted therapies in sarcoma subtypes.
Main Methods:
- Staining of 230 sarcoma tumors using SP142 and SP263 assays for PD-L1.
- Evaluation of PD-L1 immunoreactivity by two clinical pathologists.
- Kaplan-Meier survival analysis to assess correlation between PD-L1 levels and patient outcomes.
Main Results:
- PD-L1 immunoreactivity (≥1%) was observed in a notable percentage of CS, LS, and UPS tumors.
- Most tumors showed ≤10% PD-L1 expression, with a subset exhibiting >50% expression.
- No significant differences in metastasis-free or overall survival were found in relation to PD-L1 immunoreactivity in tumor or immune cells across subtypes.
Conclusions:
- Current data does not support establishing clear PD-L1 cutoff values for sarcoma treatment response.
- Patients with high tumor cell PD-L1 expression (>50%) using the SP263 assay represent a potential cohort for future ICI treatment trials.
- Further research is needed to determine the efficacy of PD1/PD-L1-targeted therapies in specific sarcoma subtypes.
