Prognostic Role Of PD-L1 Expression Research Articles

Prognostic role of PD-L1 expression in head and neck squamous cell carcinoma: An institutional experience from India

BackgroundSquamous cell carcinoma accounts for > 90% of Head and neck cancers and has a poor 5-year survival rate of only 50%. Immunosuppressive agents like PD-L1 inhibitors have been found to improve survival in many tumour types, including advanced/recurrent head and neck squamous cell carcinoma (HNSCC). The PD-L1 expression in this tumour can also predict clinical outcome. However, this fact still remains to be proven. AimThe aim was to study the expression of PD-L1 in HNSCC, correlate with clinicopathological parameters and outcome. Material and methodThis prospective study was conducted between March 2021 to June 2023 in department of Pathology of a tertiary care centre located in northern India. A total of 65 histologically confirmed cases of HNSCC were included. Expression of PD-L1 was determined by immunohistochemistry. The combined positive (CPS) and tumour proportion (TP) scores were calculated. The results were correlated with clinicopathological parameters and outcome using appropriate statistical tools. ResultsConsidering CPS, 42 (64.6%) cases showed expression of PD-L1. A high score of ≥ 20% was seen in 10 cases (15.4%). PD-L1 expression did not correlate with any of the clinical parameters including age, gender, addiction, site, TNM stage and HPV status. Conventional HNSCC had significantly higher expression of PD-L1. The cases with positive PD-L1 expression had a higher mean survival and a lower mortality, but the difference was not statistically significant. ConclusionPD-L1 expression is more likely to be seen in conventional HNSCC histomorphology. PD-L1 expression is a predictor of better prognosis in HNSCC.

The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases

BackgroundMerkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles.MethodsData from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan–Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant.ResultsA total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%.ConclusionsThis is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates.

Tumor Infiltrating Lymphocytes (TILS) and PD-L1 Expression in Breast Cancer: A Review of Current Evidence and Prognostic Implications from Pathologist's Perspective.

With the rise of novel immunotherapies able to stimulate the antitumor immune response, increasing literature concerning the immunogenicity of breast cancer has been published in recent years. Numerous clinical studies have been conducted in order to identify novel biomarkers that could reflect the immunogenicity of BC and predict response to immunotherapy. In this regard, TILs have emerged as an important immunological biomarker related to the antitumor immune response in BC. TILs are more frequently observed in triple-negative breast cancer and HER2+ subtypes, where increased TIL levels have been linked to a better response to neoadjuvant chemotherapy and improved survival. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in breast cancer is observed in about 10-30% of cases and is extremely variable based on tumor stage and molecular subtypes. Briefly, TNBC shows the highest percentage of PD-L1 positivity, followed by HER2+ tumors. On the other hand, PD-L1 is rarely expressed (0-10% of cases) in hormone-receptor-positive BC. The prognostic role of PD-L1 expression in BC is still controversial since different immunohistochemistry (IHC) clones, cut-off points, and scoring systems have been utilized across published studies. In the present paper, an extensive review of the current knowledge of the immune landscape of BC is provided. TILS and PD-L1 expression across different BC subtypes are discussed, providing a guide for their pathological assessment and reporting.

PD-L1 and survival in oral cavity squamous cell carcinoma

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.

Prognostic role of PD-L1 expression in patients with advanced renal cell carcinoma (RCC) treated with sunitinib.

603 Background: the prognosis and treatment of advanced RCC has improved over the last decade due to a number of effective anti-angiogenic and immune checkpoint inhibitors (ICPI) therapies. Certain clinical factors, such as low Karnofsky status (≤ 70%); less than a one year period from diagnosis to treatment administration; low serum hemoglobin; high corrected serum calcium; high lactate dehydrogenase; elevated neutrophil count or platelet count exceeding the upper limit of the normal range, have been able to stratify patients into three distinct prognostic groups: favorable (zero risk factors), intermediate (one to two), and poor risk (more than two). Nowadays, the relationship between PD-L1 expression with treatment response and the survival rate of RCC is a current topic of interest. Methods: a retrospective analysis of 182 patients with advanced RCC who received sunitinb in a single Institution has been conducted with the aim of analyzing PD-L1 as a prognostic factor. To carry out the immunohistochemical analysis, microscopy samples have been treated with the PD-L1 IHC 22C3 pharmDx assay, which is intended to measure the percentage of PD-L1 expression in the primary tumor tissue. Results: a total of 65 patients with primary tumor tissue sampling, who were never treated with (ICPI), were analyzed. Among these, 95% were considered as intermediate or poor risk and 47% had PD-L1 expression. The results have shown that PD-L1 expression is associated with worse progression-free survival (PFS) and overall survival (OS). In patients with no expression of PD-L1, the median PFS was 16.89 months (95% confidence interval 11.0 – 40.87 months) and 12.61 months for those with some % of PD-L1 expression (4.43 – 53.09). (χ² = 1.16; Pr &gt; χ² = 0.20). Likewise, the median OS was 42.28 months (13.76 – 68.13) for patients with no expression of PD-L1 and 24.60 months for those with some % of PD-L1 expression (13.76- not reached) ( χ ² = 0.12; Pr &gt; χ ² = 0.73). Conclusions: patients treated with sunitinib who express PD-L1, have shown shorter PFS and OS. Its validation as an independent prognostic factor, with regard to other standard clinical parameters, must be considered in order to develop a more tailored approach to treatment decision.

Abstract P4-08-04: PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease

Abstract Background: Targeting the PD-L1/PD-1 axis has proved to be effective in various cancers, including promising data for metastatic TNBC pts. The evaluation of PD-L1 expression is limited by the lack of standardized methods. Here we sought to evaluate the prognostic role of PD-L1 expression in a large cohort of patients with non-metastatic TNBC treated with standard therapy. Methods: Consecutive patients diagnosed with stage I-III TNBC (ER and PgR &amp;lt;10%, HER2 0/1+ or ISH non amplified) between May 2012 and December 2015 and treated at the Istituto Oncologico Veneto of Padova were included. All patients received treatment with surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (when indicated). For each case, one FFPE tumor slide was stained for PD-L1 with the PD-L1 IHC 73-10 Research Use Only assay developed by Agilent Technologies and one slide was stained for cytokeratins with MNF116 (to distinguish MNF116+ tumor cells from MNF116- stromal cells). Digital slides were evaluated by a specifically-developed Visiopharm® software application. Following alignment of the PD-L1 and MNF116 digital slides, the software analyzed PD-L1 expression on tumor cells (% of positively stained tumor cells/total tumor cells) and stromal cells (% of positively stained stromal cells/total stromal cells). Disease-free survival (DFS) was calculated from diagnosis to relapse or death. In survival analyses, PD-L1 was evaluated as continuous and categorical variable. Results: 265 TNBC pts were evaluated. Median PD-L1 was 2.6% (Q1-Q3 0%-18.6%) on tumor cells and 5.2% (Q1-Q3 0.2%-25.4%) on stromal cells. PD-L1 levels on tumor and stromal cells were positively correlated (spearman's 0.938, p&amp;lt;0.001). For further analyses, PD-L1 on stromal cells was considered. Higher PD-L1 was associated with age &amp;lt;50 yrs (p=0.011), Grade 3 (p=0.003) and Ki67 &amp;gt;30% (p=0.005). Lower PD-L1 was observed in lobular and apocrine tumors (p=0.001).Cox model for DFS showed HR=0.99 (95%CI 0.97-1.00, p=0.059) for every 1% PD-L1 increment. 3-yrs DFS was 86% for pts with PD-L1&amp;gt;20% (n=88, 29%) vs 75% for pts with PD-L1&amp;lt;20% (n=177, 71%): HR 0.52, 95%CI 0.28-0.97, p=0.039. PD-L1 at 20% cut-off maintained prognostic value in multivariate model including stage (HR 0.48, 95%CI 0.25-0.89, p=0.021). Of the 265 pts included, 108 received neoadjuvant chemotherapy (NACT). Of the 78 pts with residual disease after NACT, 61 had pre- and post-NACT samples evaluable for PD-L1. PD-L1 increased from pre- to post-NACT: median 2.7% (Q1-Q3 0%-26.9%) vs 20.1% (Q1-Q3 5.9%-41.4%), p&amp;lt;0.001. Pts with PD-L1&amp;gt;20% post-NACT showed improved DFS: 3-yrs DFS 68% vs 43% (HR 0.44, 95%CI 0.20-0.96, p=0.039), whereas PD-L1 pre-NACT did not show significant association with DFS in this subgroup (HR 0.47, 95%CI 0.23-1.40, p=0.218). Conclusions: PD-L1 expression evaluated with a software-assisted method was prognostic for stage I-III TNBC pts treated with standard therapy. The significant increase of PD-L1 on residual disease post-NACT supports the rationale to evaluate the efficacy of anti-PD-L1 drugs in this high-risk population. Citation Format: Dieci MV, Orvieto E, Tsvetkova V, Griguolo G, Miglietta F, Bonaguro S, Tasca G, Giorgi CA, Cumerlato E, Guarneri V, Conte P. PD-L1 expression and prognosis in triple negative breast cancer (TNBC): An analysis of 265 patients (pts) treated with standard therapy for stage I-III disease [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-04.

The prognostic role of PD-L1 expression according to MSI status in stage III colon cancer after curative resection.

555 Background: Tumors expressing PD-L1 can render immune inactivated via triggering of PD-1 receptor on T cells with various pathways. Based on these mechanism, the blockade PD-1/PD-L1 pathway based been used as a therapeutic target for metastatic CRC. In the present study, we evaluated the prognostic role of PD-L1 expression associated with microsatellite status in surgically resected stage III colon cancer patients. Methods: PD-L1 expression was performed by immunohistochemistry from 182 stage III colon cancer patients after curative resection. Using the immunohistochemical stain, percentages of PD-L1 positive tumor cells and staining intensity were evaluated and categorized as ‘strong’ and ‘weak’ positive group. Clinical and histopathologic parameters including of MSI status and survival outcomes were analyzed with IDO expression which stands for the suppressive immune environment. Results: Strong PD-L1 expression was observed in 29% of all patients. PNI and lymphocyte response response were more frequently shown in strong PD-L1 patients. Among these patients, MSI was shown in 23 patients (12%). Although there was no significant difference between MSI and PD-L1 status, strong PD-L1 tended to better OS in MSS colon cancer (P = 0.056). In contrast, strong PD-L1 expression significantly correlated with significantly worse prognosis in disease free survival (P = 0.001) and overall survival (P &lt; 0.001) than weak PD-L1 expression inMSI patients regardless of adjuvant chemotherapy. In MSI patients, the strong IDO expression was tended to be more frequently shown in strong PD-L1 expression patients (36.4%) than weak PD-L1 expression patients (14.3%). Conclusions: The expression of PD-L1 is differently affected on the survival according to the status of microsatellite. There is no significant relationship between the expression of PD-L1 and prognosis in MSS stage III colon cancer patients. However, in MSI colon cancer which has been well known as a highly immunogenic property, strong PD-L1 expression is significantly associated with poor prognosis on survival outcomes reflecting of immunosuppressive microenvironment in curative resected stage III colon cancer patient.

The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: A systematic review and meta-analysis

BackgroundProgrammed death-ligand 1 (PD-L1) is an immune checkpoint that is primarily located on the surface of tumor cells. PD-L1 expression detected by immunohistochemistry (IHC) assays has been widely studied to predict survival outcomes in head and neck squamous cell carcinoma (HNSCC) recently. We aimed to review comprehensively the prognostic role of PD-L1 expression for survival in HNSCC. MethodsWe systematically searched PubMed, Embase, Web of Science, Cochrane Library and Scopus to identify studies investigating the prognostic role of PD-L1 expression in HNSCC. All studies published before March 31, 2018 were screened. Included studies were assessed using the Quality in Prognosis Studies (QUIPS) tool. Data were extracted and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), disease-specific survival (DSS) were combined and presented as hazard ratios (HR) with 95% confidence interval (CI) using the generic inverse-variance method. ResultsTwenty-three studies with 3105 patients were analysed. The overall positive rate of PD-L1 in HNSCC was 0.42 (95% CI: 0.36–0.48). There was no significant difference between PD-L1-positive and -negative HNSCC patients in OS (HR: 0.98; 95% CI: 0.71–1.37; p = 0.93), DFS (HR: 1.07; 95% CI: 0.68–1.70; p = 0.76), and DSS (HR: 0.90; 95% CI: 0.63–1.29; p = 0.56). An improved PFS was observed in patients with positive PD-L1 expression (HR: 0.71; 95% CI: 0.55–0.93; p = 0.01). In patients with low CD8+ tumor-infiltrating T cells, a poorer OS was detected in patients with positive PD-L1 expression (HR: 1.90; 95% CI: 1.07–3.36; p = 0.03). Patients with HPV-positive HNSCC were associated with increased PD-L1 expression (OR: 1.99; 95% CI: 1.50–2.64; p < 0.001). However, PD-L1 expression showed no significant benefit on OS in HPV-positive HNSCC (HR: 1.04; 95% CI: 0.65–1.65; p = 0.88). ConclusionsPD-L1 expression detected by IHC was not recommended to predict survival in HNSCC patients. However, the positive PD-L1 expression might predict better PFS in patients with advanced HNSCC. The combined effects of PD-L1 expression and CD8+ tumor-infiltrating T cells should be further elucidated.

The prognostic role of programmed cell death-ligand 1 expression in non-small cell lung cancer patients: An updated meta-analysis

BackgroundProgrammed cell death-ligand 1 (PD-L1) seemed to be associated with the outcomes of non-small cell lung cancer. However the prognostic role of PD-L1 expression among NSCLC remained unclear and inconsistent. The aim of the study set out to evaluate the correlation between PD-L1 expression and the prognosis of patients that developed NSCLC. MethodsIdentified literatures were extracted of various electronic databases and a meta-analysis was performed to evaluate the prognostic role of PD-L1 among NSCLC patients. ResultsTotally 25 studies from 11 countries containing 5861 patients were included in the meta-analysis. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were 1.176 (95% CI: 1.016–1.361, P = 0.029) and 1.170 (95% CI: 0.984–1.392, P = 0.076), respectively. High PD-L1 expression on NSCLC tissue was also related with worse OS among Asian patients (HR = 1.381, 95% CI: 1.127–1.629, P = 0.002), adenocarcinomas (HR = 1.899, 95% CI: 1.306–2.762, P = 0.001) and poor PFS in non-Asian patients (HR = 1.695, 95% CI: 1.158–2.480, P = 0.002). Sensitivity analysis indicated that removal of any particular included literature won't affect the pooled results. Publication bias among the studies was not significant neither. ConclusionsPD-L1 expression is a prognostic factor related with poor survival among patients that developed NSCLC.

Prognostic role of tumoral PDL1 expression and peritumoral FoxP3+ lymphocytes in vulvar melanomas

The prognostic role of PDL1 expression, CD8+ and FoxP3+ lymphocytes in vulvar melanomas has not been studied. We correlated PDL1 expression and CD8+ and FoxP3+ immune infiltrates with clinicopathologic variables and patient outcomes in a series of 75 vulvar melanomas. Tumoral PDL1 expression (>5%) was seen in 23% of cases. By Fisher exact test, PDL1 expression and peritumoral FoxP3+ lymphocytes significantly correlated with less disease-specific death. By linear regression analysis, correlations between tumoral PDL1 expression with the density of tumoral CD8+ and peritumoral CD8+ lymphocytes, tumoral FoxP3+ with tumoral CD8+ lymphocytes, and peritumoral FoxP3+ with peritumoral CD8+ lymphocytes were observed. By univariate analyses, tumor thickness >4 mm predicted poorer progression-free survival, melanoma-specific survival, and overall survival. PDL1 expression >5% and peritumoral CD8+, peritumoral FoxP3+, and tumoral FoxP3+ lymphocytes correlated with better overall survival. By multivariate analyses, high peritumoral FoxP3+ lymphocytes independently predicted better melanoma-specific survival (P = .023), and tumor thickness independently predicted poorer progression-free survival (P = .05) and overall survival (P = .039). In conclusion, our study shows that, independent from tumor thickness, an increased density of peritumoral FoxP3+ lymphocytes may positively impact survival in a subset of vulvar melanomas. Tumoral PDL1 expression correlated with tumoral as well as peritumoral CD8+ and FoxP3+ lymphocytes, supportive of an adaptive immune response. Although the frequency of PDL1 expression is low in vulvar melanoma, its expression may identify a subset of vulvar melanoma that might respond to immunotherapy.

Prognostic value of PD-L1 expression in resected lung adenocarcinoma and potential molecular mechanisms.

Background: The prognostic role of PD-L1 expression in surgically resected lung adenocarcinoma (ADC) remains controversial. The present study was aimed to clarify the role of PD-L1 expression in predicting prognosis and to investigate its biological function in ADC.Materials and Methods: The association between PD-L1 expression and clinical outcomes in patients with resected ADC was analyzed using immunohistochemistry (IHC) in our cohort (n=104), externally validated by a meta-analysis of 13 published studies. The biological role of PD-L1 in ADC was explored using gene set enrichment analysis (GSEA).Results: Positive PD-L1 expression in tumor cells was observed in 38.5% (40/104). High PD-L1 expression levels were significantly correlated with poor overall survival (P=0.008). Furthermore, the meta-analysis also showed that positive PD-L1 expression was associated with shorter OS than negative PD-L1 expression (HR= 1.75, 95% CI: 1.26-2.42; P<0.001). In subgroup analysis stratified according to ethnicity, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for Asian populations (HR= 2.11, 95% CI: 1.48-3.02; P<0.001), but not for non-Asian populations (HR=1.16, 95% CI: 0.63-2.11, P=0.64). The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with positive lymph node metastasis (OR=1.74, 95% CI: 1.23-2.46; P=0.002) and male (OR=1.56, 95% CI: 1.02-2.37; P=0.04). GSEA revealed PD-L1 expression levels positively correlated with immune process or immune-related pathways.Conclusion: PD-L1 expression is an important negative prognostic factor in resected ADC. This finding has important implications for immunotherapy targeting the PD-1/PD-L1 pathway in patients with resected ADC.

1061P - The prognostic role of PD-L1 expression in tumor and immune cells in oral cavity squamous cell carcinoma

1061P - The prognostic role of PD-L1 expression in tumor and immune cells in oral cavity squamous cell carcinoma

Independent prognostic role of PD-L1expression in patients with esophageal squamous cell carcinoma.

Accumulating evidence has shown that PD-L1 expression is associated with clinicopathological features in various human malignancies. We searched for correlations between PD-L1 expression and clinicopathological data in esophageal squamous cell carcinoma (ESCC) patients. PD-L1 expression in primary tumors from 278 patients was evaluated using immunohistochemistry (IHC) in ESCC tissue microarray. Survival curves were constructed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. Overall, tumoral PD-L1 expression (≥10%, 20% or 30% as cut-off value) was associated with favorable DFS and OS upon multivariate analysis. When the patients stratified into stage I-II (168, 60.4%) and stage III-IV (110, 39.6%), or with lymph node metastasis (133, 47.8%), the prognostic role was not consistent. In patients with stage I-II disease, tumoral PD-L1 expression (≥5%, 10%, 20% or 30%) was associated with better DFS and OS upon multivariate analysis. In patients without lymph node metastasis, tumoral PD-L1 expression (≥1%, 5%, 10%, 20%, or 30%) was associated with improved DFS and OS in univariate or multivariate analysis. However, PD-L1 expression was not correlated with prognosis in patients with stage III-IV disease or with lymph node metastasis. Our results for the first time showed the prognostic role of tumoral PD-L1 expression was variable in different stages and lymph node status of ESCC. Tumoral PD-L1 expression was independent favorable predictor in ESCC patients with Stage I-II disease or without lymph node metastasis, not in stage III-IV or lymph node metastasis.

Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases

IntroductionProgrammed death ligand 1 (PD-L1) expression determined by immunohistochemistry (IHC) may serve as a predictive biomarker for anti–PD-1/PD-L1 therapies; however, little is known about intertumoral heterogeneity of PD-L1 expression determined by IHC in lung adenocarcinomas (ADCs), and there have been conflicting results on the prognostic role of PD-L1 expression in ADCs. MethodsPD-L1 expression was evaluated in resected stage II and III ADCs by using various cutoffs and correlated with clinicopathologic parameters and survival. PD-L1 expression was also compared between the primary tumor and lymph node metastases. ResultsThere were 109 study cases. PD-L1 expression was seen in 56 (51%), 43 (39%), and 19 (17%) when cutoffs of at least 1%, at least 5%, and at least 50%, respectively, were used. Abundant intratumoral CD8-positive T cells were a significant predictor of the expression in the primary tumor, with cutoffs of 1% and 5% (p < 0.001 for both) by multivariate analysis, whereas they were a nonsignificant predictor of the expression with a 50% cutoff (p = 0.076). PD-L1 expression was concordant between the primary tumor and nodal metastasis in most of the cases, but it was discrepant in up to 38%. The discrepancy was attributed in part to different predominant histologic patterns between the primary and metastatic tumors. In the entire cohort, PD-L1 expression with all cutoffs had no bearing on 5-year recurrence-free survival. ConclusionsPD-L1 expression is associated with abundant intratumoral CD8-positive T cells in resected ADCs, suggesting a predictive role of PD-L1 expression in anti–PD-1/PD-L1 therapies; however, the possible intertumoral heterogeneity of PD-L1 expression raises a concern about selecting the most appropriate sample for PD-L1 IHC.

Prognostic Role of Programmed Death Ligand-1 Expression in Breast Cancer: A Systematic Review and Meta-Analysis.

Cancer therapies that target the PD-1/PD-L1 pathway are in ongoing phase I/II clinical trials for several tumor types. However, the prognostic value of PD-L1 expression in breast cancer is unclear. We assessed the prognostic role of PD-L1 expression in breast cancer. We searched Medline/PubMed for eligible studies of the association between PD-L1 expression and patient survival in breast cancer published before 7 December 2015. The effect size was the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS). Odds ratios (OR) with 95% CIs were also extracted to evaluate associations between PD-L1 expression and patient clinicopathological features. We included five studies with 7,802 total patients in this meta-analysis. The pooled OR associated high PD-L1 expression with predictors of poor-prognosis: high tumor grade, negative ER status, negative PR status, positive HER2 status and lymphovascular invasion. High PD-L1 protein expression was associated with shorter OS (HR = 3.22, 95% CI: 1.86-5.59; P < 0.0001), shorter RFS (HR = 1.38, 95% CI: 1.03-1.86; P = 0.03) and shorter MFS (HR = 3.33, 95% CI: 2.30-4.82; P < 0.00001); whereas high PD-L1 mRNA expression was associated with longer OS (HR = 0.86, 95% CI: 0.75-1.00; P = 0.05) and longer RFS (HR = 0.57, 95% CI: 0.36-0.91; P = 0.02). The findings of these studies were significantly heterogeneous; the results should be interpreted cautiously. In breast cancer, high PD-L1 protein expression appears to be a negative prognostic factor, whereas high PD-L1 mRNA expression appears to be a favorable prognostic factor.

Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-Analysis.

Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression. To investigate the prognostic role of PD-L1 expression in patients affected by renal cell carcinoma (RCC). MEDLINE/PubMed, the Cochrane Library, and ASCO University were searched for studies investigating the prognostic role of PD-L1 expression in RCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Six studies and 1323 cases were included in the final analysis. PD-L1 was expressed in 24.2% of clear cell tumors compared to 10.9% of non-clear cell tumors (p = 0.002). In the overall population, a higher level of PD-L1 expression increased the risk of death by 81% (HR; 1.81, 95% CI 1.31-2.49; p < 0.001). When the analysis was restricted to cases evaluated by immunohistochemistry alone, the higher expression of PD-L1 more than doubled the risk of death (HR; 2.05, 95% CI 1.38-3.05; p < 0.001). In clear cell histology, higher PD-L1 expression increased the risk of death by 53% (HR; 1.53, 95% CI 1.27-1.84; p < 0.001), while in metastatic patients, the evaluation of PD-L1 expression on primary tumors revealed that it retains its prognostic role (HR; 1.45, 95% CI 1.08-1.93; p = 0.01). Significant heterogeneity has been identified among the included studies. As a consequence, cautious interpretation of the results is recommended. This meta-analysis indicates that a higher level of PD-L1 expression is a negative prognostic factor in RCC. Its validation as an independent prognostic factor compared to other traditionally used clinical parameters in localized or advanced disease is recommended.

F17 - Prognostic role of PD-L1 expression in renal cell carcinoma. A systematic review and meta-analysis

F17 - Prognostic role of PD-L1 expression in renal cell carcinoma. A systematic review and meta-analysis

2649 Prognostic role of PD-L1 expression in renal cell carcinoma (RCC): A systematic review and meta-analysis

2649 Prognostic role of PD-L1 expression in renal cell carcinoma (RCC): A systematic review and meta-analysis

High ratio of programmed cell death protein 1 (PD-1)+/CD8+ tumor-infiltrating lymphocytes identifies a poor prognostic subset of extrahepatic bile duct cancer undergoing surgery plus adjuvant chemoradiotherapy

Background and purposeThis study investigated the prognostic role of PD-L1 expression, PD-1+ tumor-infiltrating lymphocytes (TILs), and the ratio of PD-1+/CD8+ TILs in extrahepatic bile duct (EHBD) cancer. Materials and methodsWe analyzed 83 patients with EHBD cancer who underwent curative surgery plus fluoropyrimidine-based chemoradiotherapy (CRT). Expressions of PD-L1, PD-1, and CD8 were assessed by immunohistochemistry. ResultsFifty-six (68%) patients were PD-L1-positive, and its lower expression level was associated with hilar tumor location (P=0.044). A higher ratio of PD-1+/CD8+ TILs was associated with poorer overall survival (OS) (P=0.032), relapse-free survival (RFS) (P=0.024), and distant metastasis-free survival (DMFS) (P=0.039) in Kaplan–Meier analyses, but survival differences were not observed according to the PD-L1 expression level. With Cox proportional hazards models, the ratio of PD-1+/CD8+ TILs was the independent prognostic factor in OS (HR 2.47, 95% CI 1.04–5.86), RFS (HR 2.41, 95% CI 1.08–5.41), and DMFS (HR 2.67, 95% CI 1.00–7.11) after adjusting for other significant clinicopathologic variables. ConclusionA strong survival impact of the ratio of PD-1+/CD8+ TILs was observed in EHBD cancer. In the poor prognostic subgroup, the blockade of the immune checkpoint in combination with conventional multimodality treatment needs to be considered.