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. 2022 Feb 11;12(2):292.
doi: 10.3390/biom12020292.

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

Yifan Zhang  1   2 , Yi Chen  2 , Andri Papakonstantinou  2   3 , Panagiotis Tsagkozis  4   5 , Christina Linder-Stragliotto  3   4 , Felix Haglund  1   2
Affiliations

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

Yifan Zhang et al. Biomolecules. .

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.

Keywords: PD-L1; chondrosarcoma; immunotherapy; liposarcoma; sarcoma; undifferentiated pleomorphic sarcoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Distribution of PD-L1 immunoreactivity in tumor and immune cells with SP142 and SP263 assays for (A) chondrosarcoma, (B) liposarcoma and (C) undifferentiated pleomorphic sarcoma.
Figure A2
Figure A2
Univariate analysis of association between clinical/tumor characteristics, PD-L1 immunoreactivity and metastasis-free survival (MFS) of (A) chondrosarcoma, (B) liposarcoma and (C) undifferentiated pleomorphic sarcoma (* = p < 0.05).
Figure A3
Figure A3
Kaplan–Meier curves depicting MFS based on PD-L1 immunoreactivity in tumor cells for (A) chondrosarcoma, (B) liposarcoma and (C) undifferentiated pleomorphic sarcoma.
Figure A4
Figure A4
Kaplan–Meier curves depicting overall survival (OS) based on PD-L1 immunoreactivity in immune cells for (A) liposarcoma and (B) undifferentiated pleomorphic sarcoma.
Figure A5
Figure A5
Kaplan–Meier curves depicting MFS based on PD-L1 immunoreactivity in immune cells for (A) liposarcoma and (B) undifferentiated pleomorphic sarcoma.
Figure 1
Figure 1
(A) Magnetic resonance imaging depicting chondrosarcoma (CS) in the humerus (arrow) and (B) histology of high-grade CS stained with (C) SP142 and (D) SP263 assays at ×200 magnification showing a higher number of cells with PD-L1 immunoreactivity using the SP263 assay. (E) Clinical and tumor characteristics of the CS cohort.
Figure 2
Figure 2
Univariate cox regression analysis of association between clinical/tumor characteristics, PD-L1 immunoreactivity and overall survival of (A) chondrosarcoma, (B) liposarcoma and (C) undifferentiated pleomorphic sarcoma (P = primary, M = metastasis, R = recurrence, * = p < 0.05). We found no significant association between PD-L1 immunoreactivity and overall survival.
Figure 3
Figure 3
Kaplan–Meier curves depicting overall survival in (A) chondrosarcoma, (B) liposarcoma and (C) undifferentiated pleomorphic sarcoma in relation to PD-L1 immunoreactivity in tumor cells, as well as data from the Cancer Genome Atlas for (D) LS and (E) UPS, showing no significant impact of PD-L1 status on overall survival. Kaplan–Meier survival analysis was performed by log-rank test.
Figure 4
Figure 4
(A) Computed tomography of liposarcoma (LS) in the neck region (arrow). (B) Histology of LS stained with (C) SP142 and (D) SP263 assays at ×200 magnification showing a higher number of cells with PD-L1 immunoreactivity using the SP263 assay. (E) Clinical and tumor characteristics of the LS cohort.
Figure 5
Figure 5
(A) Magnetic resonance imaging of undifferentiated pleomorphic sarcoma (UPS) in the thigh (arrow) and (B) histology of UPS stained with (C) SP142 and (D) SP263 assays at ×200 magnification showing a higher number of cells with PD-L1 immunoreactivity using the SP263 assay. (E) Clinical and tumor characteristics of the UPS cohort.
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