Clinicopathological and prognostic significance of PD-L1 expression in sarcoma

Abstract

Programmed cell death-ligands 1 (PD-L1) is a key immune checkpoint protein and a promising therapeutic target for malignancy tumor immunotherapy. The prognostic value of PD-L1 in patients with bone and soft tissue sarcoma remains controversial. Therefore, this meta-analysis is conducted to evaluate the associations of PD-L1 expression with overall survival (OS), progression-free survival (PFS), and clinicopathological characteristics of sarcomaA comprehensive literature search of PubMed, Web of Science, Embase, and Cochrane Library was conducted for relevant studies. A total of 14 studies published from 2013 to 2017 were included. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from included studies to assess the association between PD-L1 expression and OS, PFS of patients with sarcoma. Other relevant data were extracted to evaluate the correlations of PD-L1 expression with risk and clinicopathological characteristics of sarcoma. Stata 12.0 software was applied to calculate the strength of association between PD-L1 expression and sarcoma.In total, 14 articles containing 15 independent studies and 1,451 patients were included in this meta-analysis. We found that the high PD-L1 expression was associated with poorer overall survival (HR 1.27, 95% CI: 0.70–1.84 P = .000) and poorer events-free survival (HR 2.05, 95% CI: 1.55–2.70, P = .000) in bone and soft-tissue sarcoma patients. Additionally, we conducted subgroup analysis according to histology type, ethnicity, target of PD-L1 assessment, cutoff, the significant correlations with poor overall survival and events-free survival were also observed. In contrast none of the clinicopathological characteristics (gender, age, tumor site, tumor grade, tumor depth, tumor necrosis rate, metastasis, recurrence, chemotherapy, radiotherapy) was found to be associated with PD-L1 expression in our analysis.The findings from this meta-analysis indicate that PD-L1 expression might be a useful predicative factor of poor prognosis for patients with bone and soft tissue sarcoma.

Prevalence of PD-L1 expression in matched recurrent and/or metastatic sarcoma samples and in a range of selected sarcomas subtypes

“…The frequency of PD-L1 expression in sarcomas reported in the literature is highly variable with incidences ranging from 0% to 65% [5,[7][8][9][10][11][12][13][14][15][16][17][18][19]. In their analysis, some of these series have combined statistical analysis of the two molecularly characteristic groups of sarcomas, that is those associated with recurrent specific genetic events (e.g.…”

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

“…We did not investigate the correlation between PD-L1 IHC expression and specific clinical pathological variables (i.e. tumour size, grade, site, patient's age, etc), as such correlation has not been previously identified (9,14) and no obvious trend was seen in our cohort (See Table 1 paediatric osteosarcomas, demonstrated that 75% of metastatic lesions but no primary osteosarcomas expressed PD-L1 (35). The same phenomenon was observed in a case of dedifferentiated chondrosarcoma, which showed absence of PD-L1 in the primary tumour and positive expression in the metastasis (36) and this has also recently been documented in a series of metastatic renal cell carcinomas (37).…”

“…Our other Rec/Met paired cases showed concordant absence of TILs at initial presentation and on the metastasis / recurrence ( Table 1). As high density TILs (specifically, CD3+/CD8+) is an independent positive prognostic factor for OS and DFS in sarcomas (10) We did not characterise subsets of TILs (ie.. CD8+, FoXP3+, etc) because this has been previously published (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and because our study focused on the possible relevance of TILs on histological H&E-stained sections. With regards to the correlation between PD-L1 and PD-1 expression this is conflicting with a study from the Cancer Genome Atlas Research Network demonstrating that PD-L1 mRNA does not correlate with PD-1 (21).…”

“…The frequency of PD-L1 expression in sarcomas reported in the literature is highly variable with incidences ranging from 0% to 65% (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In their analysis, some of these series have combined statistical analysis of the two molecularly characteristic groups of sarcomas, that is those associated with recurrent specific genetic events (e.g.…”

“…The predictive and prognostic significance of PD-L1 expression in sarcomas has also been reviewed including its correlation with PD-1 expression, and the presence and degree of tumour-infiltrating lymphocytes (TILs) (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”