Correlation between PD-L1 expression ON CTCs and prognosis of patients with cancer: a systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Kong D
PROVIDER: S-EPMC8218685 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library. The baseline information extracted were: authors, year of publication, country where the study was performed, study design, sample size, follow-up time, baseline characteristics of the study population, pathologic data, overall survival (OS). A total of 15 eligible studies covering 3291 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The analysis showed that the expression level of PD-L1 was associated with the overall survival in GC (Hazard Ratio, HR = 1.46, 95%CI = 1.08-1.98, P = 0.01, random-effect). In addition to the above, subgroup analysis showed that GC patients with deeper tumor infiltration, positive lymph-node metastasis, positive venous invasion, Epstein-Barr virus infection positive (EBV+), Microsatellite Instability (MSI) are more likely to expression PD-L1. The results of this meta-analysis suggest that GC patients, specifically EBV+ and MSI, may be prime candidates for PD-1 directed therapy. These findings support anti-PD-L1/PD-1 antibodies as a kind of immunotherapy which is promising for GC.
| S-EPMC5552131 | biostudies-literature
Project description:BackgroundBreast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis.MethodsWe will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extracted directly from the studies, if available. Methodological quality and bias of included studies will be assessed using a standardized checklist and overall quality of evidence will be assessed through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. If meta-analysis is possible, the measures of association will be calculated using bivariate random-effects models. Statistical heterogeneity will be evaluated with I2 statistics and explored through sensitivity analysis.DiscussionImmunomodulation seems to be a promising strategy in solid tumors. Breast cancer is the most common malignancies in women worldwide, and one of the leading causes of cancer death. PD-1 and PD-L1 are key physiologic suppressors of the cytotoxic immune reaction.Trial registrationSystematic review registration: CRD42019121118 (PROSPERO).
| S-EPMC7098137 | biostudies-literature
Project description:BackgroundNovel immunotherapeutic strategies targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis are often administered when metastatic tumors show PD-L1 positivity, even in the setting of lung cancer brain metastasis (LCBM). However, biological differences exist between primary tumors and metastatic sites. The objective of this study was to analyze rates of PD-L1 receptor discordance between primary tumors and LCBM.MethodsA systematic review of studies of biopsied or resected LCBM evaluating PD-L1 discordance published in the Medline database was performed using PRISMA guidelines. Weighted random effects models were used to calculate pooled estimates.ResultsSix full-text articles (n = 230 patients) with a median of 32 patients in each study (range: 24-73) reported PD-L1 receptor expression analyses of both primary lung tumors and brain metastases and met inclusion criteria. The pooled estimate for tumor cell (TC) PD-L1 receptor discordance between primary tumors and LCBM was 19% (95% confidence interval [CI]: 10-27%). For PD-L1 receptor expression in tumor-infiltrating lymphocytes (TIL), the weighted pooled estimate for discordance was 21% (95% CI: 8-44%). For primary versus LCBM, the positive rates by expression levels of <1%, 1-50%, and >50% were 52% (95% CI: 30-73%) versus 56% (95% CI: 34-76%), 30% (95% CI: 22-40%) versus 20% (95% CI: 10-35%), and 15% (95% CI: 6-36%) versus 22% (95% CI: 15-31%) (P = .425), respectively.ConclusionsPD-L1 discordance occurs in ~20% of LCBM, with the greatest discordance in the 1-50% expression category. Although controversial, confirming discordance might be important for selection of immune checkpoint inhibitor therapy and in the analysis of patterns of failure after treatment.
| S-EPMC8704382 | biostudies-literature
Project description:The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS). A total of 5 studies containing 2,546 cases were included in the analysis. The combined hazard ratio (HR) and its 95% confidence interval (CI) for OS were 1.76 (95% CI 1.09-2.82; P=0.02) for patients with tumors exhibiting PD-L1 overexpression. The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis, higher histological grades, estrogen receptor (ER)-negativity, and triple-negative breast cancer (TNBC). Our findings indicate that PD-L1 expression is a promising biomarker for the prognosis of breast cancer, and may be helpful to clinicians aiming to select the appropriate immunotherapy for breast cancer.
| S-EPMC5458212 | biostudies-literature
Project description:: Antibodies against programmed death-1 (PD-1), and its ligand, (PD-L1) have been approved recently for the treatment of small-cell lung cancer (SCLC). Although there are previous reports that addressed PD-L1 detection on tumour cells in SCLC, there is no comprehensive meta-analysis on the prevalence of PD-L1 expression in SCLC. We performed a systematic search of the PubMed, Cochrane Library and EMBASE databases to assess reports on the prevalence of PD-L1 expression and the association between PD-L1 expression and overall survival (OS). This meta-analysis included 27 studies enrolling a total of 2792 patients. The pooled estimate of PD-L1 expression was 26.0% (95% CI 17.0-37.0), (22.0% after removing outlying studies). The effect size was significantly heterogeneous (I2 = 97.4, 95% CI: 95.5-98.5, p < 0.0001).Positive PD-L1 expression was a favourable prognostic factor for SCLC but not statistically significant (HR = 0.86 (95% CI (0.49-1.50), p = 0.5880; I2 = 88.7%, p < 0.0001). Begg's funnel plots and Egger's tests indicated no publication bias across included studies (p > 0.05). Overall, there is heterogeneity in the prevalence of PD-L1 expression in SCLC tumour cells across studies. This is significantly moderated by factors such as immunohistochemistry (IHC) evaluation cut-off values, and assessment of PD-L1 staining patterns as membranous and/or cytoplasmic. There is the need for large size, prospective and multicentre studies with well-defined protocols and endpoints to advance the clinical value of PD-L1 expression in SCLC.
| S-EPMC7693331 | biostudies-literature
Project description:Purpose: To investigate the correlation between the expression of PD-L1, SOCS3 and immune-related biomarkers CD276, CD4, CD8 in hepatocellular carcinoma (HCC) and further determine the relationship with clinicopathologic characteristics and the prognostic value of their co-expression in HCC patients. Methods: We assessed the expression of PD-L1, CD276, SOCS3, CD4 and CD8 by immunohistochemistry in tumor tissue from 74 HCC patients who underwent curative hepatectomy. Results: High expression of PD-L1 was significantly associated with high Edmondson grade (p<0.01) and elevated enzyme (p=0.037); high expression of CD276 was significantly correlated with high Edmondson grade (p=0.021); high expression of SOCS3 was significantly associated with age (p=0.026) and tumor size (p=0.041), while PD-L1 showed no significant correlation. The expression of PD-L1, CD276, SOCS3 protein and other clinicopathological factors (sex, vascular invasion, tumor number, tumor capsule, pT stage, liver cirrhosis, HBsAg, TBiL, AFP) showed no significant correlation (p>0.05). High expression of CD8 was respectively significantly associated with worse overall survival (OS) (p=0.002). There was no significantly difference between CD4 and CD8 high-expression and overall survival (OS) (p=0.100). Both high expression of PD-L1 (p=0.003) and low expression of SOCS3 (p=0.015) was significantly associated with worse overall survival (OS). But CD276 only had a trendency (p=0.166). Additionally, multivariate Cox regression models implied that PD-L1, SOCS3, as well as both CD4 and CD8 was an independent prognostic factor for OS (p<0.05). Furthermore, HCC patients with PD-L1 low-expression and SOCS3 high-expression had a better prognostic according to the different pT stages (p<0.05). Conclusions: We for the first time demonstrated that PD-L1 and SOCS3 were independent prognostic factor for HCC patients. Co-expression of low PD-L1 and high SOCS3 could be a better predictive marker for HCC patients.
| S-EPMC7391185 | biostudies-literature
Project description:BackgroundInhibitors of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PD-L1) checkpoint have been approved for metastatic triple negative breast cancer (mTNBC) in patients positive for PD-L1 expression. Negative results from the recent phase III trials (IMPassion131 and IMPassion132) have raises questions on the efficacy of PD-1/PD-L1 checkpoint inhibitors and the predictive value of PD-L1 expression. Here we attempt to systematically analyze the biomarker value of PD-L1 expression for predicting the response of PD-1/PD-L1 checkpoint inhibitors in mTNBC.Materials and methodsPubMed database was searched until Dec 2021 for studies evaluating PD-1/PD-L1 checkpoint inhibitors plus/minus chemotherapy in mTNBC. Outcome of interest included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Review Manager (RevMan) version 5.4. was used for data-analysis.ResultsIn total, 20 clinical trials comprising 3962 mTNBC patients (ICT: 2665 (67%); CT: 1297 (33%) were included in this study. Overall ORR was 22% (95%CI, 14-30%) and significant improvement was observed for PD-L1+ patients (ORR 1.78 [95%CI, 1.45-2.19], p<0.00001) as compared to PD-L1- cohort. Pooled outcome also indicated a significant 1-year PFS and 2-year OS advantage for patients with PD-L1 expression (1-year PFS: ORR 1.39 [95%CI, 1.04-1.85], p=0.02; I2 = 0%; 2-year OS: (ORR 2.47 [95%CI, 1.30-4.69], p=0.006; I2 = 63%). Subgroup analysis indicated that PD-L1 expression can successfully predict tumor response and 2-year OS benefit in mTNBC patients regardless of the type of investigating agent, line of treatment administration, and to some extent the type of treatment. Biomarker ability of PD-L1 expression to predict 1-year PFS was slightly better with pembrolizumab (p=0.09) than atezolizumab (p=0.18), and significantly better when treatment was administered in the first-line setting (OR 1.38 [95%CI, 1.02-1.87], p=0.04) and chemotherapy was added (OR 1.38 [95%CI, 1.02-1.86], p=0.03). Immune-related toxicity of any grade and grade≥3 was 39% (95%CI, 26%-52%) and 10% (95%CI, 8%-13%), respectively.ConclusionsPD-L1 expression can predict objective response rate and 2-year OS in mTNBC patients receiving PD-1/PD-L1 checkpoint inhibitors. One-year PFS is also predicted in selected patients. PD-L1 expression can be a useful biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in mTNBC.
| S-EPMC10027008 | biostudies-literature
Project description:Programmed death ligand 1 (PD-L1) has been investigated in various types of cancer; however, the role of PD-L1 expression in breast cancer remains controversial. We performed a systematic review and meta-analysis to assess the association of PD-L1 expression with clinicopathological variables, overall survival (OS), and disease-free survival (DFS) in invasive breast cancer. A total of 965 articles were included from CINAHL, Embase, PubMed, and Scopus databases. Of these, 22 studies encompassing 6468 cases of invasive breast cancer were included in the systematic review, and 15 articles were included in the meta-analysis. PD-L1 expression was associated with age ≥ 50 years, lymph node status-negative, progesterone receptor-negative, Ki67 ≥ 20%, and human epidermal growth factor receptor 2 (HER2)-negative. PD-L1 positivity was associated with worse OS (hazard ratio, HR, 2.39; 95% confidence interval, CI, 1.26-3.52; p =< 0.000); however, there was no significant improvement in DFS (HR 0.17; 95% CI -0.12-0.46; p =< 0.252). PD-L1 positivity was significantly associated with the clinicopathological characteristics of favorable and unfavorable prognoses. However, the final clinical outcome was associated with lower OS and had no significant association with DFS.
| S-EPMC8656531 | biostudies-literature
Project description:The present study aimed to investigate the clinicopathological significance of programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin-embedded tissue specimens and 50 para-carcinoma tissue specimens. The associations of PD-L1 and PD-1 expression with clinicopathological characteristics and prognosis of ECC patients were explored. Positive rates of PD-L1 and PD-1 expression were increased in ECC tissues compared with those in the corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation with patient age, sex or histological grade, but was significantly correlated with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and lymphatic metastasis were significantly associated with the survival time of patients. Further multivariate analysis revealed the PD-L1 expression was an independent prognostic factor of patients with ECC. These preliminary results suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker for ECC patients, and that PD-L1 immunodetection may be used as an independent factor to evaluate the prognosis of ECC patients.
| S-EPMC5494943 | biostudies-other
Project description:We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients' outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.
| S-EPMC7764288 | biostudies-literature