Incidence and Prognostic Significance of PD-L1 Expression in High-Grade Salivary Gland Carcinoma.
Ontology highlight
ABSTRACT: Objective
PD-L1 is one of the predictors of immunotherapy efficacy. Our goal was to analyze its expression and prognostic significance in high-grade salivary gland carcinoma (SGC).Methods
PD-L1 expression was evaluated using paraffin-embedded specimens from patients with surgically treated high-grade SGC, and it was scored by the tumor proportion score (TPS), combined positive score (CPS), and immune cell (IC) score. Associations between clinicopathological variables, disease-free survival (DFS), overall survival (OS) and PD-L1 expression were assessed.Results
TPS≥1% occurred in 47 patients with an incidence of 43.1%, and it was significantly related to an advanced tumor stage. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year DFS rates were 36%, 26%, and 13%, respectively, and the difference was significant. In patients with TPS<1%, TPS ranging from 1% to 20%, and TPS≥20%, the 5-year OS rates were 49%, 24%, and 13%, respectively, and the difference was significant. CPS≥1 occurred in 87 patients with an incidence of 79.8%. IC scores of 0, 1, 2, and 3 were noted in 24 (22.0%), 37 (33.9%), 31 (28.4%), and 17 (15.6%) patients, respectively. Both CPS and IC scores had no impact on DFS or OS.Conclusions
The expression of PD-L1 in tumor cells of high-grade SGCs was not uncommon, and it was significantly associated with tumor stage. PD-L1 expression in tumor cells rather than in immune cells indicated a poor prognosis.
SUBMITTER: Fang Q
PROVIDER: S-EPMC8427307 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundAlthough programmed cell death-ligand 1 (PD-L1) has been recognized as a potential marker in several cancers, the relationship between PD-L1 expression and survival in patients with salivary gland carcinoma (SGC) has remained unclear. We aimed to evaluate the association of PD-L1 expression with clinicopathological features and prognosis in SGC patients.MethodsThe databases Ovid Medline, PubMed, Scopus, and EMBASE were searched for relevant studies that detected PD-L1 expression in SGC. The meta-analysis was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA), and the reporting recommendations for tumor marker prognostic studies (REMARK) was used to assess the quality of research eligible for this meta-analysis. Included studies were assessed using the Quality in Prognosis Studies (QUIPS) tool. Odds ratios (ORs) with 95% confidence interval (CI) were calculated to estimate the correlation between PD-L1 expression and clinicopathological features. Hazard ratios (HRs) with 95% CI were applied to assess the association between PD-L1 expression and survival outcomes of patients.ResultsA total of ten studies (including 952 patients with SGC) were evaluated. The meta-analysis showed that positive PD-L1 expression in SGC was significantly associated with male patients, older age, Tumor stage, lymph node metastasis, high pathological grade, and non-adenoid cystic carcinoma subtype. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival and disease-free survival. There was no significant correlation between PD-L1 expression and progression-free survival or disease-specific survival of SGC patients.ConclusionAccording to the meta-analysis, positive PD-L1 expression may play an important role as an effective marker of poor prognosis in patients with SGC. However, large-scale, prospective investigations are still needed to confirm the findings. The assessment of PD-L1 expression may aid in the personalized management of SGC.
| S-EPMC9321421 | biostudies-literature
Project description:Although immune checkpoint inhibitors (ICIs) are effective in some patients with salivary gland carcinoma (SGC), biomarkers which predict the efficacy and prognosis of SGC patients treated with pembrolizumab have not been identified. We conducted a multi-institutional retrospective cohort study to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with recurrent and/or metastatic SGC and to determine optimal cut-off values of the combined positive score (CPS) and tumor proportion score (TPS) as numerical expression levels of programmed death-ligand 1 (PD-L1), which predict the efficacy of pembrolizumab. Furthermore, we investigated the association of patient characteristics and hematological markers with clinical outcomes, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). From 2016 to 2021, 27 patients were included in the analysis. ORR of SGC was 25.9%. Optimal cut-off values of CPS and TPS were 15 and 25%, respectively. ORRs of CPS-high and TPS-high were 55.6 and 75.0%, respectively, and significantly higher than those of CPS-low and TPS-low. Furthermore, patients with a low platelet-lymphocyte ratio (PLR) had a significantly longer PFS. No grade 4 or greater adverse events were observed. This study demonstrated the efficacy and safety of pembrolizumab monotherapy and identified optimal cut-off values of CPS and TPS.
| S-EPMC11347672 | biostudies-literature
Project description:Purpose:The expression of programmed death-ligand 1 (PD-L1) is common in various solid human cancers and it is an important therapeutic target. However, the expression pattern, clinical significance and potential mechanism of PD-L1 in hypopharyngeal squamous cell carcinoma (HSCC) are still lacking. Methods:PD-L1 expression in HSCC tumor tissues and paired adjacent hypopharyngeal mucosal tissues was detected using immunohistochemistry assay, and the clinical significance of PD-L1 in HSCC was characterized. In vitro assays including cell viability assays, migration assays, invasion assays as well as Western blot assays were performed to illuminate the biological functions and underlying molecular mechanisms of PD-L1 in HSCC development. Results:PD-L1 expression was detected in HSCC samples but we found no positive expression in matched normal hypopharyngeal mucosal tissues. The levels of PD-L1 expression were significantly correlated with advanced clinical progression and poor patient survival. Multivariable analysis of Cox model showed that PD-L1 expression was an independent predictor for the prognosis of HSCC patients. Functional experiments showed that the ectopic expression of PD-L1 markedly influenced the proliferation, migration and invasion of FaDu cells in vitro. Mechanistically, investigations demonstrated that PD-L1 could promote the epithelial-mesenchymal transition of FaDu cells. Meanwhile, PD-L1 knockdown inhibited, while PD-L1 overexpression activated the Akt-mTOR signaling pathway in FaDu cells. The EMT induced by PD-L1 overexpression could be reversed by the Akt inhibitor. Conclusion:In summary, the expression of PD-L1 can act as a significant biomarker for the adverse clinicopathological features and poor prognosis of patients with HSCC. PD-L1 can promote the proliferation, migration and invasion of FaDu cells and consequently enhance the aggressiveness. Moreover, PD-L1 induces EMT through AKT-mTOR signaling pathway. These suggest that PD-L1 has important tumor-intrinsic functions independent of its immunopathogenic effects.
| S-EPMC7373417 | biostudies-literature
Project description:Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.
| S-EPMC5444735 | biostudies-literature
Project description:BackgroundHigh-grade salivary gland cancer is a distinct clinical entity that has aggressive disease progression and early systemic spread. However, because of the rarity of the disease, the clinical outcomes, prognostic factors and clinical decision on the optimal treatments have not been fully understood.MethodsIn this study, we retrospectively analyzed the clinical data of 124 patients with high-grade salivary gland cancers and performed multivariate survival analyses to evaluate the clinico-pathological factors affecting the treatment outcomes.ResultsThe 5-year disease-specific survival was 63.4% in patients with high-grade salivary gland cancers. Among the clinico-pathological factors, presence of lymph node metastasis (hazard ratio 5.63, 95% confidence interval 2.64-12.03, P < 0.001) and distant metastasis (hazard ratio 4.59, 95% confidence interval 2.10-10.04, P < 0.001) at diagnosis were the most potent unfavorable prognostic factors. Importantly, patients with early-stage disease (T1-2N0M0) showed apparently a relatively excellent prognosis (93.2% 5-year disease-specific survival); meanwhile N (+) and M1 status at diagnosis resulted in dismal outcomes (44.6 and 21.1% 5-year disease-specific survival, respectively). On comparing surgery alone as a treatment modality, surgery plus postoperative radiation significantly benefited the patients, but the difference between adjuvant radiation and chemoradiation was not found to be significant. Pathological subtypes of high-grade salivary gland cancers were not significantly associated with prognosis.ConclusionsDespite of an overall unfavorable prognosis in high-grade salivary gland cancer, patients with early-stage disease are expected to have excellent prognosis (over 90% survival rates) with surgery plus adjuvant radiation, which may implicate the patients' consultation, therapeutic decision making, and the need for early detection of the disease.
| S-EPMC6011413 | biostudies-literature
Project description:ObjectivesSince large cell neuroendocrine carcinoma (LCNEC) is a relatively rare histologic type of primary lung cancer, little is known about the immunological status of patients with LCNEC. We aimed to clarify the expression and prognostic impact of programmed cell death ligand 1 (PD-L1), CD8, CD4, and Forkhead box protein P3 (Foxp3) in LCNEC.MethodsWe retrospectively analyzed PD-L1, CD8, CD4, and Foxp3 expressions in 95 surgically resected LCNEC. PD-L1 positive staining was determined in tumors with more than 1% of tumor cells stained to any intensity, and CD8, CD4, and Foxp3 positivity was determined in tumors with more than 5% of lymphocytes stained.ResultsPositive expression of PD-L1, CD8, CD4, and Foxp3 was observed in 70 (74%), 52 (55%), 76 (80%), and 43 (45%) tumors, respectively. The expression of PD-L1 was significantly correlated with positive lymphatic permeation. Positive correlations were mutually observed among tumor infiltrating immune cells. Univariate and multivariate analyses showed that positive pleural invasion and Foxp3 negative expression were independent unfavorable prognostic factors for overall survival (OS). Advanced pathological stage, positive pleural invasion, CD4 negative expression in cancer stroma, and Foxp3 negative expression were identified as independent unfavorable prognostic factors for recurrence free survival (RFS).ConclusionsFoxp3 positive tumor infiltrating lymphocytes (TILs) were an independent favorable prognostic factor for both OS and RFS, whereas CD4 positive TILs were an independent significant unfavorable prognostic factor for RFS. The high frequency of PD-L1 expression could support the use of anti-programmed cell death 1 antibody in the treatment of LCNEC.
| S-EPMC6220228 | biostudies-literature
Project description:AimsAntibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma.MethodsPD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset.ResultsPD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS (p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets (p = 0.02 and p < 0.0001, respectively).ConclusionsDespite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity.
| S-EPMC4811475 | biostudies-literature
Project description:The advent of checkpoint immunotherapy, particularly with programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, has provided ground-breaking results in several advanced cancers. Substantial efforts are being made to extend these promising therapies to other refractory cancers such as gliomas, especially glioblastoma, which represents the most frequent and malignant glioma and carries an exceptionally grim prognosis. Thus, there is a need for new therapeutic strategies with related biomarkers. Gliomas have a profoundly immunosuppressive tumour micro-environment and evade immunological destruction by several mechanisms, one being the expression of inhibitory immune checkpoint molecules such as PD-L1. PD-L1 is recognised as an important therapeutic target and its expression has been shown to hold prognostic value in different cancers. Several clinical trials have been launched and some already completed, but PD-1/PD-L1 inhibitors have yet to show convincing clinical efficacy in gliomas. Part of the explanation may reside in the vast molecular heterogeneity of gliomas and a complex interplay within the tumour micro-environment. In parallel, critical knowledge about PD-L1 expression is beginning to accumulate including knowledge on expression levels, testing methodology, co-expression with other checkpoint molecules and prognostic and predictive value. This article reviews these aspects and points out areas where biomarker research is needed to develop more successful checkpoint-related therapeutic strategies in gliomas.
| S-EPMC9298327 | biostudies-literature
Project description:The response rate to checkpoint inhibitors for women with high-grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is modest, and development of predictive biomarkers is needed. The main focus has been on tumor cell PD-L1 expression, but its assessment alone is insufficient for patient selection in most malignancies. We mapped the presence of macrophages (CD68 and CD163) and lymphocytes (CD3) located within the tumor epithelium, the cell type-specific expression of PD-L1 and PD-1, and their impact on 5-year overall survival (OS) in a consecutive cohort of 130 women diagnosed with advanced HGSC between 2011 and 2015. PD-L1 was expressed mainly by macrophages (not by tumor cells) and PD-1 by lymphocytes. Women with higher CD3, PD-L1, and PD-1 expression had improved OS (P?=?0.03, P?=?0.007, and P?=?0.02, respectively). In the external data set (203 women), high expression of CD274 (encoding PD-L1) was associated with improved OS (P?=?0.03), in accordance with our results. Furthermore, higher CD163 expression was associated with better outcome in women with no residual tumor after primary surgery (P?=?0.02). Thus, women with greater lymphocyte tumor infiltration had better outcome and PD-L1/PD-1 expression, regardless of PD-1/PD-L1 being markers for immune suppressive pathways, conferred a survival benefit in our cohort. Our results highlight that tumor immunity may be harnessed in subsets of HGSC.
| S-EPMC7320055 | biostudies-literature
Project description:BACKGROUND:Despite the observed association of increased PD-L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands-PD-L1 and PD-L2-is insufficiently understood. Aim of the study was to investigate whether the alterations of PD-L1 and PD-L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD-L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD-L2 expression with histomorphologic and prognostic tumor parameters. METHODS:PD-L2 mRNA expression was analyzed in tumors and healthy oral mucosa specimens and in corresponding peripheral blood samples of 48 OSCC patients and 26 healthy controls using RT-qPCR. A cutoff point (COP) was determined and a chi-square test (?2 test) was carried out. Survival analysis of PD-L2 and previously reported PD-L1 expression data was performed using Kaplan-Meier analysis (Log-rank test). RESULTS:PD-L2 expression in tissue samples was significantly (P < 0.001) higher in OSCC patients compared to healthy controls. A significant association of PD-L2 expression above the COP (positive) with malignancy was ascertained (P < 0.001). A significant (P = 0.01) association of previously reported PD-L1 expression rates in peripheral blood with survival could be shown. CONCLUSION:Peripheral blood PD-L1 expression might be a prognostic marker for OSCC patients and a possible parameter to monitor immune dysfunction in malign diseases. In the peripheral blood, PD-L1 might be more relevant for immune tolerance than PD-L2. Local PD-L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.
| S-EPMC6434218 | biostudies-literature