Programmed Cell Death Ligand 1 Expression Status Research Articles

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

PD-L1 expression in patients with non-small-cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population.

Programmed cell death-ligand 1 (PD-L1) expression is a well-established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD-L1 expression status. Understanding the clinical features of patients with distinct PD-L1 levels is crucial for personalized treatment approaches. Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non-small-cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD-L1 expression: PD-L1 Tumor Proportion Score (TPS) negative, 1-50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD-L1 expression ≥50%. PD-L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD-L1 expression, low and high PD-L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD-L1 expression, although it did not reach statistical significance (p = 0.06). Although sex and genomic alterations are associated with PD-L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD-L1 expression significantly.

Clinical status and perspective on the application of immunotherapy combined with chemotherapy in advanced non-small cell lung cancer: a review.

The therapeutic landscape of advanced non-small cell lung cancer (NSCLC) has been significantly improved by developing immunotherapy represented by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICI). Furthermore, immunotherapy combined with chemotherapy is an essential treatment strategy for driver-negative advanced NSCLC, especially in a population with PD-L1 <50%, and leads to long-term survival in the entire population regardless of the PD-L1 expression status. However, specific challenges must be overcome, including how to use immunotherapy with chemotherapy in clinics. Furthermore, the application of immunotherapy with chemotherapy in populations such as elderly patients and patients with brain metastases, oligometastases, epidermal growth factor receptor (EGFR) gene mutation, anaplastic lymphoma kinase (ALK) gene rearrangements, and other driver gene-positive populations must be further explored. The biomarkers associated with immunotherapy and chemotherapy are still unclear, and the search for predictive biomarkers can contribute toward more precise and personalized immunotherapy. Furthermore, treatment strategies after immunotherapy and chemotherapy resistance are of significant focus clinically, and clinical studies with multiple combination therapy strategies are ongoing. Therefore, based on the reported status of immunotherapy combined with chemotherapy for advanced NSCLC, this study conducted a comprehensive literature review by searching keywords "PD-1 and PD-L1, immune checkpoint inhibitor (ICI), and NSCLC" in MEDLINE, major conferences, and major clinical research projects to elucidate the therapeutic efficacy of immunotherapy combined with chemotherapy as the current first-line treatment approach for various types of NSCLC patients. Additionally, it addresses several pressing challenges associated with immunotherapy combined with chemotherapy, including enhancing treatment response and survival rate in specific patient populations and identifying potential biomarkers.

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL).

The phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 <50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program. PEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan-Meier method), response to therapy, and tolerability. Until February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5-9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate. The results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily.

Abstract 5146: Clinical significance of inter-assay discrepancy in PD-L1 expression evaluation for the efficacy of pembrolizumab in advanced NSCLC patients with high PD-L1 expression

Abstract Introduction: The expression of programmed cell death ligand-1 (PD-L1) is a predictive biomarker for the efficacy of pembrolizumab in advanced non-small cell lung cancer (NSCLC). While several assays have been approved for evaluating PD-L1 expression status, the inter-assay discordances are observed. The clinical significance of these discrepancies is still unclear. Methods: We retrospectively reviewed treatment-naïve NSCLC patients with available PD-L1 expression status by both 22C3 and SP142 assays. Among these patients, efficacy analysis was performed in those with PD-L1 tumor proportion score (TPS) ≥ 50% (22C3) who received the first-line pembrolizumab monotherapy. Additionally, we conducted RNA-sequence analysis in the patients with TPS ≥ 50% to investigate the distinct immune profiles with the inter-assay discordance. Results: A total of 611 patients were evaluated for PD-L1 expression status by both assays. Of 198 patients with TPS ≥ 50%, 91 (46%) had TC score ≤ 1 (SP142, i.e., inter-assay discrepancy). In 52 patients who received the first-line pembrolizumab monotherapy, the efficacy in patients with the inter-assay discrepancy was significantly lower than those without the discrepancy (shown in Table). While there was no difference in tumor microenvironments such as the tumor-infiltrating lymphocytes, the transcriptome analysis revealed significantly more CD274 splicing variants with aberrant 3’-terminal sequences in tumors with the inter-assay discrepancy than those without discrepancy, leading to the suppressed PD-1/PD-L1 pathway in those with the discrepancy. Conclusion: The inter-assay discrepancy in the PD-L1 expression status on tumor cells between the 22C3 and SP142 assays, reflecting an imbalance of the CD274 splicing variants, could be a primary-resistance mechanism to the pembrolizumab monotherapy in highly PD-L1-expressing NSCLCs. PD-L1(22C3) Discrepancy Pts. ORR(%) p value Median PFS(months) 95%CI p value TPS ≥ 50% yes 17 18 &amp;lt; 0.001 3.2 0.8–5.5 &amp;lt; 0.001 no 35 83 8.3 5.7–24.2 Citation Format: Jun Miyakoshi, Jumpei Kashima, Masayuki Shirasawa, Masahiro Torasawa, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Tatsuya Yoshida, Yasushi Goto, Hidehito Horinouchi, Kouya Shiraishi, Takashi Kohno, Noboru Yamamoto, Yasushi Yatabe, Yuichiro Ohe. Clinical significance of inter-assay discrepancy in PD-L1 expression evaluation for the efficacy of pembrolizumab in advanced NSCLC patients with high PD-L1 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5146.

Correlation of CT parameters and PD-L1 expression status in gastric cancer.

We aimed to explore the correlation between routine computed tomography (CT) imaging features and programmed cell death ligand-1(PD-L1) expression status in gastric cancer and evaluate the predictive value of imaging parameters for this immunotherapy biomarker. Patients with gastric adenocarcinoma who underwent abdominal CT three-stage enhanced scan and PD-L1 immunohistochemical testing before treatment were retrospectively examined. All diagnoses were confirmed through pathology. According to the expression status of PD-L1, they were divided into the positive (CPS ≥ 5) or negative group (CPS < 5). Baseline CT imaging features were collected. Diagnostic performances of the different variables were evaluated using receiver operating characteristic (ROC) curve. In total, 67 patients (17 women and 50 men; mean age: 59.55 ± 10.22years) with gastric adenocarcinoma were included in the study. The overall stages, probability of maximum lymph node short diameter > 1cm and peak of lesion enhancement occurring in the arterial phase were statistically significant between the two groups (p < 0.05). Moreover, the arterial enhancement fraction (AEF) was significantly higher in the positive group than that in the negative group (p < 0.05), and ROC curve analysis showed that the AEF exhibited a high evaluation efficacy (area under the curve [AUC] = 0.724 [95% confidence interval (CI): 0.602-0.826]). The combined parameters had the best diagnostic efficacy (AUC = 0.825 [95%CI: 0.716-0.933]), sensitivity (75.00%), and specificity (81.40%). These findings confirm a correlation between CT imaging features and PD-L1 expression status in gastric cancer, and AEF may help evaluate high PD-L1 expression and select patients suitable for immunotherapy.

Standardized and quality-assured predictive PD-L1 testing in the upper gastrointestinal tract. German version

As aresult of the high approval dynamics and the growing number of immuno-oncological therapy concepts, the complexity of therapy decisions and control in the area of carcinomas of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD‑1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken aposition on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.

Cost-Effectiveness Analysis of Atezolizumab versus Platinum-Based Chemotherapy as First-Line Treatment for Patients with Unresectable Advanced Non-small Cell Lung Cancer with PD-L1 Expression Status in Japan.

Atezolizumab has demonstrated safety and efficacy in patients with metastatic non-small cell lung cancer (NSCLC) in the IMpower110 trial. The aim of this study was to evaluate thecost-effectiveness of atezolizumab as the first-line treatment for patients with unresectable advanced NSCLC, including programmed cell death ligand-1 (PD-L1)-positive probability testing, from the perspective of healthcare costs in Japan. A cost-effectiveness analysis model for atezolizumab, including PD-L1-positive probability testing, was used toconstruct a partitioned survival model with three health states. To assess the robustness, aprobabilistic sensitivity analysis (PSA) was conducted. The acceptable probability wasdefined asthe probability of willingness-to-pay (WTP) over theincremental cost-effectiveness ratio (ICER). Multiple repetitions at WTP thresholds were calculated by continuously reducing the atezolizumabprice. The ICER per quality-adjusted life year (QALY) for atezolizumab therapy only for patients with high PD-L1 expressioncompared to platinum-based chemotherapy for all patients was 31,975,792 yen per QALY. This is higher than the WTP threshold of 15,000,000yen. If the cost of atezolizumab were reduced to 54% of theoriginal cost (563,917 yen), the strategy of using atezolizumab for patients with high PD-L1 could become more cost-effective. The results indicated that atezolizumab was not cost-effective compared to platinum-based chemotherapy as a first-line treatment for patients with unresectable advanced NSCLC. However, we suggest that the price of atezolizumab shouldbe reduced to 54% of theoriginal cost to meet the WTP threshold of 15,000,000 yen per QALY.

Standardized and quality-assured predictive PD-L1 testing in the upper gastrointestinal tract.

As a result of the high approval dynamics and the growing number of immuno-oncological concepts, the complexity of treatment decisions and control in the area of cancers of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD-1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand 1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken a position on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.

The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment

IntroductionNonmuscle invasive bladder cancers (NMIBC) are common tumors diagnosed in older individuals and men (median age: 69 years). Immunotherapy is a treatment option in cases resistant to Bacillus-Calmette-Guerin (BCG) therapy. We aimed to evaluate the prognostic role of programmed-cell-death ligand (PD-L)-1 (PD-L1), PD-L2, and signal transducer and activator of transcription 3 (STAT3) expressions, which are closely related to immune mechanisms, in the response to BCG treatment of NMIBC. MethodsThe data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials. ResultsThe mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively). ConclusionsThe success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.

Prognostic impact of soluble PD-L1 derived from tumor-associated macrophages in non-small-cell lung cancer.

Programmed cell death-ligand 1 (PD-L1) on tumor cells can be degraded to soluble form (sPD-L1) and enter circulation, however, the clinical significances of sPD-L1 in peripheral blood remains to be elucidated in non-small-cell lung cancer (NSCLC). We monitored plasma sPD-L1 levels during perioperative periods and evaluated PD-L1-positive cells in tumor tissues in patients with operable NSCLC. Then the correlation between preoperative plasma sPD-L1 levels and relapse-free survival (RFS) was analyzed retrospectively. In patients who underwent radical surgery (n = 61), plasma sPD-L1 levels (median; 63.5pg/mL) significantly increased 1month after surgery (72.2pg/mL, P < 0.001). The combined score of PD-L1-positive cells including tumor cells and tumor-associated macrophages (TAMs) was significantly associated with preoperative plasma sPD-L1 levels. In patients with high levels of preoperative plasma sPD-L1, the probability of 5-year RFS was significantly poor for patients with low PD-L1 expression intensity of tumor cells (tcPD-L1) compared with those with high tcPD-L1 (33.3% vs. 87.5%, respectively, P = 0.016; 95% CI, 0.013-0.964). In former group, PD-L1-positive TAMs were markedly infiltrating compared with those from latter group (246.4 vs. 76.6 counts/mm2, respectively, P = 0.003). In NSCLC, plasma sPD-L1 can reflect the accumulation of PD-L1-posotive TAMs, not just PD-L1-positive tumor cells. In patients with high levels of preoperative plasma sPD-L1, the prognoses after surgery depends on which PD-L1-positive cells, tumor cells or TAMs, are the primary source of the sPD-L1. Thus, measuring both plasma sPD-L1 levels and PD-L1 expression status of tumor cells and TAMs is of benefit for assessment of postoperative prognosis in operable NSCLC.

Comparative efficacy and safety of PD-1/PD-L1 inhibitors in triple negative breast cancer: a systematic review and network meta-analysis of randomized controlled trials

BackgroundTriple-Negative Breast Cancer (TNBC) is a lethal subtype of breast cancer with limited treatment options. The purpose of this Network Meta-Analysis (NMA) is to compare the efficacy and safety of inhibitors of programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in treating TNBC.MethodsOur search strategy was used in six databases: PubMed, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature database, Embase, Scopus, and Web of Science up to November 2nd, 2022, as well as a thorough search in the most used trial registries. We included phase II and III randomized controlled trials that looked at the efficacy of PD-1/PD-L1 inhibitors in the treatment of TNBC and reported either Overall Survival (OS), Progression-Free Survival (PFS), or pathological Complete Response (pCR). The risk of bias was assessed utilizing Cochrane's risk of bias 2 tool, and the statistical analysis was performed using a frequentist contrast-based method for NMA by employing standard pairwise meta-analysis applying random effects model.Results12 trials (5324 patients) were included in our NMA including seven phase III trials. Pembrolizumab in a neoadjuvant setting achieved a pooled OS of 0.82 (95% Confidence Interval (CI) 0.65 to 1.03), a PFS of 0.82 (95% CI 0.71 to 0.94) and a pCR 2.79 (95% CI 1.07 to 7.24) compared to Atezolizumab’s OS of 0.92 (95% CI 0.74 to 1.15), PFS of 0.82 (95% CI 0.69 to 0.97), and pCR of 1.94 (95% CI 0.86 to 4.37). Atezolizumab had less grade ≥ 3 adverse events (OR 1.48, 95% CI 0.90 to 2.42) than Pembrolizumab (OR 1.90, 95% CI 1.08 to 3.33) in the neoadjuvant setting.ConclusionsPD-1/PD-L1 inhibitors exhibited varying efficacy in terms of OS, PFS, and pCR. They were associated with an increase in immune-related adverse effects. When used early in the course of TNBC, PD-1/PD-L1 inhibitors exert their maximum benefit. Durvalumab as a maintenance treatment instead of chemotherapy has shown promising outcomes. Future studies should focus on PD-L1 expression status and TNBC subtypes, since these factors may contribute to the design of individualized TNBC therapy regimens.Systematic review registration PROSPERO Identifier: CRD42022380712.

Abstract 2180: The PD-L1 protein expression in Chinese patients with advanced esophageal cancers: a multi-center retrospective study

Abstract Introduction: Programmed cell death ligand-1 (PD-L1) is the ligand of programmed cell death-1 (PD-1), a member of the immunoglobulin gene superfamily that plays a role in programmed cell death. Accumulating evidence of anti-PD-1 therapy has showed improved survival benefit for esophageal cancer (EC) patients. PD-L1 has emerged as a crucial predictor for efficacy of immunotherapy. However, the understanding of PD-L1 as a biomarker is complicated by various immunohistochemistry platforms, PD-L1 antibodies, scoring systems, and cut-offs for immunotherapy. Although PD-L1 expression has been widely investigated, the real-world PD-L1 expression status in Chinese patients with advanced EC nationwide with unified testing platform, antibody, scoring system and cut-off is largely unrevealed. Methods: The present study was a nationwide multi-center retrospective analysis of data from six centers in China from August 9, 2021, to February 28, 2022. Patients with histologically or cytologically confirmed diagnoses of advanced EC were included. The primary outcome was the prevalence of high PD-L1 expression in patients with advanced EC. Immunohistochemical analysis of PD-L1 expression was performed by using the PD-L1 IHC 22C3 pharmDx assay in EC specimens. PD-L1 protein expression was assessed by using a combined positive score (CPS). The CPS≥ 10 was defined as a high PD-L1 high expression. The Chi-square test, Fisher’s exact test, or Wilcoxon rank sum test was used to compare the PD-L1 prevalence across demographic, clinicopathologic parameters, treatment status and other biomarkers. Results: Out of 488 enrolled patients with advanced EC, 482 patients were included in the final analysis. For all testing EC patients, 207 patients (42.9% [95% CI 38.48-47.50]) were PD-L1 high expression (CPS≥10). Between the PD-L1 high (CPS≥10) group and PD-L1 low (CPS&amp;lt;10) group, there were statistically significant differences in gender (P=0.046), alcohol consumption (P = 0.011), distant metastatic lesion number of patients with stage IV (P = 0.032), surgery (P = 0.012), systemic therapy (P = 0.004), and chemotherapy (P=0.004). Conclusion: In summary, the prevalence of high PD-L1 expression (CPS≥10) in Chinese patients with advanced EC in real-world setting using 22C3 assay is consistent with previous data in global clinical trials. Our findings of the related clinicopathological and treatment features to the PD-L1 expression can provide supplementary information for decision-making of immunotherapy and facilitate the better understanding of mechanism underlying PD-L1 and anti-tumor immunity. Citation Format: Liyan Xue, Jiaqi Wang, Dong Kuang, Jingping Yun, Yuan Li, Lili Jiang, Daoyuan Wu, Pei Duan, Shixun Lu, Yan Jin, Du He, Jing Qian, Wenmin Tang, Yan Wang, Jielin Li, Jianming Ying. The PD-L1 protein expression in Chinese patients with advanced esophageal cancers: a multi-center retrospective study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2180.

Self-supervised contrastive learning using CT images for PD-1/PD-L1 expression prediction in hepatocellular carcinoma.

Programmed cell death protein-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) expression status, determined by immunohistochemistry (IHC) of specimens, can discriminate patients with hepatocellular carcinoma (HCC) who can derive the most benefits from immune checkpoint inhibitor (ICI) therapy. A non-invasive method of measuring PD-1/PD-L1 expression is urgently needed for clinical decision support. We included a cohort of 87 patients with HCC from the West China Hospital and analyzed 3094 CT images to develop and validate our prediction model. We propose a novel deep learning-based predictor, Contrastive Learning Network (CLNet), which is trained with self-supervised contrastive learning to better extract deep representations of computed tomography (CT) images for the prediction of PD-1 and PD-L1 expression. Our results show that CLNet exhibited an AUC of 86.56% for PD-1 expression and an AUC of 83.93% for PD-L1 expression, outperforming other deep learning and machine learning models. We demonstrated that a non-invasive deep learning-based model trained with self-supervised contrastive learning could accurately predict the PD-1 and PD-L1 expression status, and might assist the precision treatment of patients withHCC, in particular the use of immune checkpoint inhibitors.

Immunohistochemical expression of PD-L1 and its correlation with microsatellite status in endometrial and ovarian clear cell carcinomas: a cross-sectional study

BackgroundClear cell carcinoma is an uncommon histologic subtype of ovarian and endometrial carcinoma with poor response to Platinium-based chemotherapy agents at high stages. Blockage of Programmed cell Death Ligand-1 (PD-L1), can be used in targeted immunotherapy. This study investigated Mismatch Repair Deficiency (MMR-D) status, PD-L1 expression, and the correlation between PD-L1 expression and microsatellite instability (MSI) status in ovarian and endometrial clear cell carcinomas.MethodsOvarian clear cell carcinoma (OCCC) (n = 28) and endometrial clear cell carcinoma (ECCC) (n = 28) samples were evaluated for PD-L1 (in tumoral and peri-tumoral inflammatory cells), MSH6 and PMS2 expression by immunohistochemistry (IHC) study. PD-L1 expression > 1% in tumor cells and > 5% in peritumoral inflammatory cells were considered positive.ResultsThe prevalence of PD-L1 expression was higher in ECCC (20/28, 71.43%) compared to OCCC tumor cells (16/28, 57.15%) (p > 0.05), while expression in peritumoral inflammatory cells was significantly higher in ECCC (25/28, 89.29%) compared to OCCC (11/28, 39.28%) (p < 0.05). MMR-D was observed in 5 cases, four OCCCs and one ECCC, among which, four (80%) showed PD-L1 expression in peritumoral inflammatory and tumor cells. The only OCCC case with extensive PD-L1 expression in tumor cells (> 50%) exhibited MSH6/MSH2 loss. No significant correlation was noted between PD-L1 expression and the pathologic stage or survival.ConclusionPD-L1 expression was significantly associated with clear cell morphology, especially in the endometrium, independent of MMR protein status.

Immunotherapy in Penile Squamous Cell Carcinoma: Present or Future? Multi-Target Analysis of Programmed Cell Death Ligand 1 Expression and Microsatellite Instability.

BackgroundPenile cancer (PC) is an extremely rare malignancy, and the patients at advanced stages have currently limited treatment options with disappointing results. Immune checkpoint inhibitors anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) are currently changing the treatment of several tumors. Furthermore, the microsatellite instability (MSI) and the deficient mismatch repair system (dMMR) proteins represent predictive biomarkers for response to immune checkpoint therapy. Until present, few data have been reported related to PD-L1 expression and MSI in PC. The main aim of our study was the evaluation of PD-L1 expression in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) in immune cells and the analysis of dMMR/MSI status in a large series of PCs.MethodsA series of 72 PC, including 65 usual squamous cell carcinoma (USCC), 1 verrucous, 4 basaloid, 1 warty, and 1 mixed (warty-basaloid), was collected. Immunohistochemistry (IHC) was performed to assess PD-L1 expression using two different anti-PD-L1 antibodies (clone SP263 and SP142 Ventana) and MMR proteins expression using anti-MLH1, anti-PMS2, anti-MSH2, and anti-MSH6 antibodies. PCR analysis was performed for the detection of MSI status.ResultsOf the 72 PC cases analyzed by IHC, 45 (62.5%) cases were TC positive and 57 (79%) cases were combined positive score (CPS) using PDL1 SP263. In our cohort, TILs were present in 62 out of 72 cases (86.1%), 47 (75.8%) out of 62 cases showed positivity to PDL1 clone SP142. In our series, 59 cases (82%) had pMMR, 12 cases (16.7%) had lo-paMMR, and only 1 case (1.3%) had MMR. PCR results showed that only one case lo-paMMR was MSI-H, and the case dMMR by IHC not confirmed MSI status.ConclusionOur findings showed that PD-L1 expression and MSI status represent frequent biological events in this tumor suggesting a rationale for a new frontier in the treatment of patients with PC based on the immune checkpoint inhibitors.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma

BackgroundPulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection.MethodsWe retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors.ResultsOverall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor.ConclusionThis study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis.Trial registration The study was approved by the Kobe City Medical Center General Hospital’s ethics board (No. 20112) on August 20, 2020.

The PD-L1 Expression Among Triple-Negative Breast Cancer Patients in Universitas Sumatera Utara Teaching Hospital, Indonesia.

The emerging role of precision medicine among in oncologic science is a potentially explorable area to solve long-standing implication of triple-negative breast cancer (TNBC)'s management, especially by identifying programmed cell death ligand-1 (PD-L1) in its population. To describe the PD-L1's expression among TNBC populations in our Indonesia-based centers. This descriptive study was conducted in the teaching hospitals of Universitas Sumatera Utara ranging from April 2019 to July 2020. Our investigation encompassed female individuals with histopathologically confirmed TNBC and complete medical record data, especially the status of PD-L1 expression to be reported in this study. We use Daco 22C3 antibodies to confirm the latter protein immunohistochemical positivity after thorough specimen preparation and staining. This study included 60 females with TNBC of which 40 participants were issued in the final report. Our populations were dominated by middle-aged individuals (41-50 years old; 45%), and remarkable presentation of LVSI, angioinvasion, or lymph-node metastatic status. In PD-L1 expression status, our study reported that 45.0% patients were confirmed with confirmed PD-L1 positivity. PD-L1 expression among TNBC patients is concordant with the global report hence anti-PD-1-based treatment trial in Asia or even Indonesia region should be considered.

Baseline PD-L1 expression and tumour-infiltrated lymphocyte status predict the efficacy of durvalumab consolidation therapy after chemoradiotherapy in unresectable locally advanced patients with non-small-cell lung cancer

BackgroundChemoradiotherapy (CRT) followed by durvalumab treatment improved prognosis in unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study aimed to evaluate whether the status of the immune-related tumour microenvironment (TME) at baseline associates with the efficacy. MethodsThis retrospective study evaluated immune-related TME factors, including programmed cell death ligand 1 (PD-L1) (clone: 22C3) expression on tumour cells and the density of CD8-positive tumour-infiltrating lymphocytes (TILs) at pre-CRT in patients with unresectable LA-NSCLC treated with CRT only (CRT alone group) and those treated with CRT followed by durvalumab (Durva group). ResultsA total of 551 patients were included (N = 113 in the Durva group). Progression-free survival (PFS) in the Durva group was significantly greater than that in the CRT alone group (not reached [NR] vs 12.9 months; p = 0.002). In the CRT alone group, neither PD-L1 expression nor TIL status affected PFS; in contrast, in the Durva group, high density of CD8-positive TILs (TILHigh ≥100/mm2) and PD-L1-positive expression (tumour proportion score ≥1%; PD-L1+) was significantly associated with longer PFS (TIL: NR vs 9.5 months; p = 0.002; and PD-L1: NR vs 7.7 months; p = 0.003). On the other hand, in patients with epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, there was no significant difference in PFS between the groups (Durva vs CRT alone: 9.9 months vs 14.0 months; p = 0.77). ConclusionsPD-L1+ and TILHigh at baseline could be predictive markers of the efficacy of CRT followed by durvalumab.

Relationship with Programmed Cell Death Ligand 1 (PD-L1) and DTI Features in Brain Metastases of Non-small Cell Lung Cancer: A Preliminary Study.

The purpose of the study was to determine DTI properties of brain metastases in subjects with Non-Small Cell Lung Carcinoma (NSCLC) to evaluate whether there was a correlation between DTI findings and Programmed Cell Death Ligand-1 (PD-L1). The study population (n:22) was assigned to PD-L1 negative (Group 1: PD-L1 expression<% 50) (n=11) or positive (Group 2: PD-L1 expression ≥%50) (n=11). We compared ADC and FA values measured from the enhanced solid metastases and peritumoral edema area with PD-L1 protein status. The mean ADC values were lower in group 2 compared to group 1. The peritumoral ADC values were higher in group 2 compared to group 1. Mean peritumoral edema FA values were lower in group 2 compared to group 1. The peritumoral edema nADC values were higher in group 2 compared to group 1. As PD-L1 expression frequency increased, ADC values in the peritumoral edema area increased and FA values decreased. We thought that the existence of PD-L1 protein does not affect ADC and FA values of brain metastasis (BM) originating from NSCLC. DTI characteristics of the peritumoral edema area could be a guide in determining the PD-L1 protein status of brain metastases of NSCLC. The relationship between PD-L1 expression status and DTI features in BM from NSCLC could help us to have an idea regarding the response to immunotherapy.