A comparative view on the expression patterns of PD-L1 and PD-1 in soft tissue sarcomas.
Soft tissue sarcomas (STSs) are heterogeneous cancers associated with poor prognosis due to high rates of local recurrence and metastasis. The programmed death receptor ligand 1 (PD-L1) is expressed in several cancers. PD-L1 interacts with its receptor, PD-1, on the surface of tumor-infiltrating lymphocytes (TILs), thereby attenuating anti-cancer immune response. Immune checkpoint inhibitors targeting this interaction have been established as effective anti-cancer drugs. However, studies on the PD-L1 and PD-1 expression status in STS are commonly limited by small sample size, analysis of single STS subtypes, or lack of combinatorial marker assessment. To overcome these limitations, we evaluated the expression patterns of intratumoral PD-L1, the number of TILs, their PD-1 expression, and associations with clinicopathological parameters in a large and comprehensive cohort of 225 samples comprising six STS subtypes. We found that nearly all STS subtypes showed PD-L1 expression on the tumor cells, albeit with a broad range of positivity across subtypes (50% angiosarcomas to 3% synovial sarcomas). Co-expression and correlation analyses uncovered that PD-L1 expression was associated with more PD-1-positive TILs (P < 0.001), higher tumor grading (P = 0.016), and worse patients' 5-year overall survival (P = 0.028). The results were in line with several publications on single STS subtypes, especially when comparing findings for STS with low and high mutational burden. In sum, the substantial portion of PD-L1 positivity, the co-occurrence of PD-1-positive TILs, and the association of PD-L1 with unfavorable clinical outcome provide rationales for immune checkpoint inhibition in patients with PD-L1-positive STS.
['Orth|Martin F|MF|', 'Buecklein|Veit Leonhard|VL|', 'Kampmann|Eric|E|', 'Subklewe|Marion|M|', 'Noessner|Elfriede|E|', 'Cidre-Aranaz|Florencia|F|', 'Romero-Pérez|Laura|L|', 'Wehweck|Fabienne Sophie|FS|', 'Lindner|Lars|L|', 'Issels|Rolf|R|', 'Kirchner|Thomas|T|', 'Altendorf-Hofmann|Annelore|A|', 'Grünewald|Thomas G P|TGP|', 'Knösel|Thomas|T|']
D000293:Adolescent D000328:Adult D000368:Aged D060890:B7-H1 Antigen D014408:Biomarkers, Tumor D015331:Cohort Studies D005260:Female D005500:Follow-Up Studies D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008875:Middle Aged D009362:Neoplasm Metastasis D011379:Prognosis D061026:Programmed Cell Death 1 Receptor D012509:Sarcoma D015996:Survival Rate D055815:Young Adult
PD-L1 PD-1 Soft tissue sarcoma Tumor-infiltrating lymphocytes Immune checkpoint inhibition