Programmed Death Ligand Research Articles

Filamentous phages as tumour-targeting immunotherapeutic bionanofibres.

Programmed cell death-ligand 1 (PD-L1) blockers have advanced immunotherapy, but their lack of tumour homing capability represents a substantial challenge. Here we show that genetically engineered filamentous phages can be used as tumour-targeting immunotherapeutic agents that reduce the side effects caused by untargeted delivery of PD-L1 blockers. Specifically, we improved biopanning to discover a peptide binding the extracellular domain of PD-L1 and another targeting both melanoma tissues and cancer cells. The two peptides were genetically fused to the sidewall protein and tip protein of fd phages, respectively. The intravenously injected phages homed to tumours and bound PD-L1 on cancer cells, effectively blocking PD-1/PD-L1 recognition to trigger targeted immunotherapy without body weight loss, organ abnormalities and haematological aberrations. The phages, cost-effectively replicated by bacteria, are cancer-targeting immunotherapeutic nanofibres that can be flexibly designed to target different cancer types and immune checkpoints.

Imaging PD-L1 in the brain-Journey from the lab to the clinic.

Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy. The aim of this study was to investigate the use of 89Zr-DFO-Atezolizumab to image the spatio-temporal distribution of PD-L1 in preclinical mouse models and in patients with newly diagnosed GBM treated with/without neoadjuvant Pembrolizumab. The immunoreactivity, binding affinity, and specificity of 89Zr-DFO-Atezolizumab were confirmed in vitro. Mice-bearing orthotopic GBM tumors or patients with newly diagnosed GBM treated with/without Pembrolizumab were intravenously injected with 89Zr-DFO-Atezolizumab, and PET/CT images were acquired 24, 48, and 72 hours in mice and at 48 and 72 post-injection in patients. Radioconjugate uptake was quantified in the tumor and healthy tissues. Ex vivo immunohistochemistry (IHC) and immunophenotyping were performed on mouse tumor samples or resected human tumors. 89Zr-DFO-Atezolizumab was prepared with high radiochemical purity (RCP > 99%). In vitro cell-associated radioactivity of 89Zr-DFO-Atezolizumab corroborated cell line PD-L1 expression. PD-L1 in mouse GBM tumors was detected with high specificity using 89Zr-DFO-Atezolizumab and radioconjugate uptake correlated with IHC. Patients experienced no 89Zr-DFO-Atezolizumab-related side effects. High 89Zr-DFO-Atezolizumab uptake was observed in patient tumors at 48 hours post-injection, however, the uptake varied between patients treated with/without Pembrolizumab. 89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.

The real-world efficacy and safety of nivolumab plus chemotherapy in patients with HER2-negative advanced gastric cancer

BackgroundThe aim of this study is to investigate the real-world efficacy and safety of nivolumab in combination with chemotherapy for patients with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC).MethodsWe enrolled patients diagnosed with unresectable advanced or metastatic GC who received nivolumab plus chemotherapy as first-line systemic treatment. The combined positive score (CPS), indicating the number of programmed cell death-ligand 1 (PD-L1)-stained cells, was utilized. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Adverse events (AEs) were graded, and treatment was ceased upon disease progression or intolerance.ResultsA total of 27 patients were included in the study, comprising 15 patients with CPS ≥ 5 and 12 patients with CPS < 5. The objective response rate (ORR) was 55.6%, with a disease control rate (DCR) of 74.1%. Patients in the CPS ≥ 5 group exhibited higher ORR and DCR compared to those in the CPS < 5 group. Median PFS and OS were 6.1 months and 14.6 months, respectively; patients with CPS ≥ 5 showed a trend towards better PFS and OS than those with CPS < 5. Most AEs were grade 1–2, with a few instances of grade 3–4 toxicities reported, including neutropenia, thrombocytopenia, diarrhea, and anemia. There were no grade 5 AEs reported in our cohort. Furthermore, 64.7% of patients received subsequent anticancer treatment following disease progression on nivolumab plus chemotherapy.ConclusionsThe results of our study demonstrate the efficacy and safety of nivolumab plus chemotherapy in real-world practice support its adoption as a new standard first-line treatment for patients with advanced HER2-negative GC, particularly those with CPS ≥ 5.

Companion diagnostics and predictive biomarkers for PD-1/PD-L1 immune checkpoint inhibitors therapy in malignant melanoma.

Programmed cell death receptor 1 (PD-1), when bound to the ligand programmed death-ligand 1 (PD-L1), can suppress cellular immunity and play a critical role in the initiation and development of cancer. Immune drugs targeting these two sites have been developed for different cancers, including malignant melanoma. The accompanying diagnostic method has been approved by the FDA to guide patient medication. However, the method of immunohistochemical staining, which varies widely due to the antibody and staining cut-off values, has certain limitations in application and does not benefit all patients. Increasing researches begin to focus on new biomarkers to improve objective response rates and survival in cancer patients. In this article, we enumerated three major groups, including tumour microenvironment, peripheral circulation, and gene mutation, which covered the current main research directions. In the future, we hope those biomarkers may be used to guide the treatment of patients with malignant melanoma.

Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients.

Hepatitis B virus (HBV) infection plays an important role in the occurrence and development of hepatocellular carcinoma (HCC), and the rate of HBV infection in liver cancer patients in China is as high as 92.05%. Due to long-term exposure to chronic antigens from the gut, the liver needs to maintain a certain level of immune tolerance, both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors. Therefore, HBV infection interacts with the tumor microenvironment (TME) through a highly complex and intertwined signaling pathway, which results in a special TME in HCC. Due to changes in the TME, tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1). Interferons, as a class of immune factors with strong biological activity, can improve the TME of HBV-HCC through various pathways. In recent years, the systematic treatment of HCC has gradually come out of the dilemma. In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs, immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC. At present, immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC, and the disease characteristics of patients included in global clinical studies are different from those of Chinese patients. Therefore, whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern. This review aims to elucidate the advances of immunotherapy for HBV related HCC patients with regard to: (1) Immunotherapy based on interferons; (2) Immunotherapy based on PD-1/L1 inhibitors; (3) Immunotherapy based on CTLA4 inhibitors; (4) Adoptive cell transfer; (5) Combination immunotherapy strategy; and (6) Shortcomings of immunotherapy.

Immune checkpoint inhibitor-associated bullous pemphigoid: Aretrospective and real-world study based on the United States Food and Drug Administration adverse event reporting system.

This study aimed to describe bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICIs) reported in the United States Food and Drug Administration adverse event reporting system (FAERS). We obtained reports of ICI-associated BP from the first quarter of 2011 to the first quarter of 2024 in the FAERS database. The reporting odds ratio (ROR) method of the disproportionality analysis was performed to assess the potential risk for ICI-associated BP. We also described the clinical characteristics of ICI-associated BP and evaluated the time to onset (TTO) of BP developed after treatment with ICIs. Eight hundred and six cases of ICI-associated BP were gathered, in which 56.58% of the patients were aged 65 years or older. The majority of patients were male, accounting for 68.49% of all cases. The prevalent potential cancer type was skin cancer (31.64%). The results of the disproportionality analysis showed that males (ROR = 2.10 [1.78-2.49]), patients aged 65 or older (ROR = 2.13 [1.79-2.55]), and patients with skin cancer (ROR = 2.08 [1.80-2.43]) were more likely to develop ICI-associated BP. In comparison to cytotoxic T-lymphocyte-associated antigen 4 inhibitor and programmed cell death ligand 1 inhibitor, programmed cell death 1 inhibitor-associated BP has a higher risk of development (ROR = 24.45 [22.52-26.56]). ICI-associated BP had a median TTO of 204 days (interquartile range 57-426 days). ICI-associated BP is a rare but important immune-related adverse event. Our study provided helpful information to help medical professionals further understand ICI-associated BP.

Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.

Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.

Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer.

Although breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC. The transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal-wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA-PD-L1/PD-L2 axis were verified by dual luciferase reporter assay. Twenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094-miR-17-5p-PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094-miR-17-5p-IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2. LINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

The Potential Role of Toxoplasma Gondii Infection in Breast Cancer Through Affecting Programmed Death-1 Genes

Background: This study aimed to evaluate the possible effects of Toxoplasma gondii infection on breast cancer through affecting the serum and expression gene level of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in breast cancer patients from Thi-qar province, Iraq. Methods: This case-control study was involved 150 patients suffering from breast cancer (BC) who were referring to general hospitals of Thi-Qar province between July to September 2023 and 150 healthy patients (non-BC). Enzyme-linked immunosorbent test (ELISA) kit was used to evaluate the anti-Toxoplasma IgG and the serum level of PD-1 and PDL-1. Furthermore, the expression level of PD-1 and PDL-1 was measured through Real-time PCR. Results: Among 150 breast cancer patients, 71 patients (47.3%) and 25 (16.6%) of healthy subjects exhibited seropositivity for anti-T. gondii IgG antibodies, resepectively. We found that the serum level and the gene expression level of PD-1 and PDL-1 were significantly higher among BC patients seropositive for T. gondii compared with BC patients who were seronegative for T. gondii antibodies (p&lt;0.05). Conclusion: These results indicated that T. gondii may play a role in the occurrence and even progression of cancer probably by elevating levels of PD-1 and PDL-1 genes. However, further studies are required to confirm these findings.

Sinulariapeptide F, a new peptide from culture broth of marine-derived fungus Simplicillium sp. SCSIO 41222.

One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy (1H, 13C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC50 value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4.

Impact of TTF-1 Expression on the Prognostic Prediction of Patients with NSCLC with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs Chemoimmunotherapy: A Multicenter, Retrospective Study.

Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%. We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy. This study included 283 of 624 patients. TTF-1-positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI): 5.0-9.4] vs 4.1 months [95% CI: 2.7-6.1], p=0.03, OS: 17.9 months [95% CI: 15.2-28.1] vs 9.4 months [95% CI: 6.3-17.0], p<0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1-positive and negative groups (PFS: 7.6 months [95% CI: 6.4-11.0] vs 6.0 months [95% CI: 3.6-12.6], p=0.59, OS: 25.0 months [95% CI: 18.0-49.2] vs 21.3 months [95% CI: 9.8-28.8], p=0.09). In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.

The Prevalence of Programmed Death Ligand-1 (PD-L1) Expression in Non-Small Cell Lung Cancer: An Experience From Tertiary Care Hospital

The Prevalence of Programmed Death Ligand-1 (PD-L1) Expression in Non-Small Cell Lung Cancer: An Experience From Tertiary Care Hospital

Anti–Programmed Death Ligand 1 Plus Targeted Therapy in Anaplastic Thyroid Carcinoma

Anaplastic thyroid carcinoma (ATC) is a rare and lethal cancer. Although progress has been made in recent years in patients with mutated BRAF tumors, those who respond initially eventually die of their disease; furthermore, there are no approved therapies for non-BRAF mutated tumors. To determine whether treatment with matched-targeted therapy plus immune checkpoint inhibitors were associated with improved overall survival (OS). A phase 2 trial at a single center, tertiary institution with parallel cohorts, assigning treatment with targeted therapy according to the tumor mutation status. Patients with mutated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mutated RAS (NRAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2). Patients without any of these variants were assigned to receive bevacizumab plus atezolizumab (cohort 3). Patients were enrolled from August 3, 2017, to July 7, 2021. All consecutive, systemic therapy-naive patients with ATC with active disease and who met eligibility criteria were considered for participation. The analysis was conducted in September 2023. Patients were assigned to targeted therapy based on the driver mutation as follow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab). All received atezolizumab. The primary outcome of the study was median OS of the entire targeted therapy cohort, compared with historical median OS of 5 months. Forty-three patients with ATC were enrolled in the targeted therapy cohorts, of which 42 were included in the primary analysis. The median OS in patients across these 3 cohorts was 19 months (95% CI, 7.79-43.24). Median OS and progression-free survival per cohort were as follows: cohort 1: 43 months (95% CI, 16-not estimable [NE]), 13.9 months (6.6-64.1); cohort 2: 8.7 months (95% CI, 5.1-37.0) and 4.8 months (1.8-14.7); cohort 3 (vascular endothelial growth factor inhibitor group): 6.21 months (4.1-NE) and 1.3 months (1.3-NE), respectively. In this nonrandomized clinical trial, atezolizumab combined with targeted therapy resulted in a longer median OS than historical landmark, achieving the study's primary end point, with cohort 1 achieving the longest OS. ClinicalTrials.gov Identifier: NCT03181100.

Clinical significance of CD155 expression in surgically resected lung squamous cell carcinoma.

Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan-Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

A photosensitive modification of recombinant Salmonella carrying shRNA-PD-L1 promotes host immunity against poorly immunogenic tumors

The tumor microenvironment (TME) exists as a hypoxic, non-inflammatory “cold” state, it is difficult for many drugs to target the aggregation and activation of the immune system. The attenuated facultative anaerobe Salmonella can be used as a tumor-targeting vector to overcome osmotic limitations and exhibit immune effects against the hypoxic characteristics of the tumor region, maximizing the diagnostic and therapeutic targeting. Here, we genetically modified the ΔphoPΔphoQ knockout strain of attenuated Salmonella enterica serovar typhimurium LH430 to carry programmed cell death ligand 1 (PD-L1) short hairpin RNA (shRNA) on a plasmid to solve the current problem of therapeutic antibodies targeting immune checkpoints in the clinic. In addition, combining the attenuated Salmonella with the photosensitizer IR780 not only allows the bacteria to aggregate and target hypoxia at the tumor site, but also the photothermal therapy for an effective tumor ablation. This approach provides a promising strategy for photothermal therapy and immunotherapy targeting deep-seated tumors.

A Multiple Targeting Genome Editing System for Remodulation of Circulating Malignant Cells to Eliminate Cancer Immunosuppression and Restore Immune Responses.

Cancer immunotherapy, which aims to eliminate cancer immunosuppression and reactivate anticancer immunity, holds great promise in oncology treatments. However, it is challenging to accurately study the efficacy of immunotherapy based on human-derived cells through animal experiments due to xenogeneic immune rejection. Herein, a personalized and precise strategy to evaluate the effectiveness of immunotherapy using the blood samples of cancer patients is presented. Through the utilization of multiple cancer-targeting delivery system decorated with the epidermal growth factor receptor (EGFR)-specific aptamer CL4 and the AXL-specific aptamer GL21.T to achieve superior efficiency in delivering the genome editing plasmid for MUC1 knockout, effective modulation on the behavior of circulating malignant cells (CMCs) is realized. After genome editing, both mucin 1 (MUC1) and programmed death-ligand 1 (PD-L1) are significantly downregulated in CMCs. The elimination of immunosuppression results in markedly enhanced secretion of pro-inflammatory anticancer cytokines encompassing interleukins 2, 12, and 15 and interferon-γ by immune cells. The study not only provides a strategy to overcome immunosuppression but also yields critical insights for personalized immunotherapy approaches.

PD-1 immunology in the kidneys: a growing relationship.

In recent years, knowledge regarding immune regulation has expanded rapidly, and major advancements have been made in immunotherapy for immune-associated disorders, particularly cancer. The programmed cell death 1 (PD-1) pathway is a cornerstone in immune regulation. It comprises PD-1 and its ligands mediating immune tolerance mechanisms and immune homeostasis. Accumulating evidence demonstrates that the PD-1 axis has a crucial immunosuppressive role in the tumor microenvironment and autoimmune diseases. PD-1 receptors and ligands on immune cells and renal parenchymal cells aid in maintaining immunological homeostasis in the kidneys. Here, we present a comprehensive review of PD-1 immunology in various kidney disorders, including renal cell carcinoma, glomerulonephritis, kidney transplantation, renal aging, and renal immune-related adverse events secondary to PD-1 immunotherapy.

Programmed Death-Ligand 1 (PD-L1) and Ki-67 Labeling Index: Correlation with Tumor Grade and Recurrence

Background: Meningiomas are common primary brain tumors with variable clinical behavior. While most are benign, a subset exhibits aggressive characteristics and a high recurrence rate. This study aimed to investigate the association of Programmed Death-Ligand 1 (PD-L1) and Ki-67 labeling index with histopathological grade and recurrence in meningioma. Methods: A retrospective study was conducted on 139 cases of meningioma diagnosed between January 2020 and December 2023. PD-L1 expression was evaluated using immunohistochemistry (IHC) and scored using the combined positive score (CPS). Ki-67 labeling index was determined as the percentage of tumor cells with positive nuclear staining. The association of PD-L1 and Ki-67 with histopathological grade and recurrence was analyzed. Results: PD-L1 expression was positive in 66.7% of cases and was significantly associated with recurrence (p = 0.006). A higher Ki-67 labeling index (&gt;4%) was observed in 68.9% of cases and was also significantly associated with recurrence (p = 0.013). No significant association was found between PD-L1 expression or Ki-67 labeling index and histopathological grade. Conclusion: PD-L1 expression and Ki-67 labeling index may serve as potential prognostic markers for predicting recurrence in meningioma. Further studies are needed to validate these findings and explore their potential therapeutic implications.

The Detailed Analysis of Polish Patients with Non-Small Cell Lung Cancer Through Insights from Molecular Testing (POL-MOL Study).

Molecular testing is recommended in patients with metastatic non-small cell lung cancer (NSCLC), but the extent of its use in Poland is unknown. The aim of the POL-MOL study was to investigate the frequency of using molecular testing in Polish patients with NSCLC. The invited Polish oncologists completed two questionnaires, and data for 1001 patients undergoing systemic treatment for NSCLC were collected. The use of molecular tests for the following genetic mutations was recorded: EGFR (del19, sub21), EGFR (other than del19/sub21), EGFR T790M, ALK (expression and rearrangement), RET, NTRK, ROS1, BRAF, HER2, and MET, as well as for immunochemical assessment of programmed cell death ligand 1 (PD-L1). Thanks to the weighting procedure, the results are representative of the population of Polish patients treated for NSCLC. Molecular tests were applied in 78% of patients with NSCL, 70% of patients with NSCLC not otherwise specified, and in 12% of patients with squamous cell carcinoma of the lung. The frequency of application increased with disease stage in all groups. In patients with squamous cell carcinoma, approximately 30% of tests for EGFR, ALK, and RET mutations were positive, which confirms the importance of testing at least a preselected subgroup of patients.

The complex role of immune cells in antigen presentation and regulation of T-cell responses in hepatocellular carcinoma: progress, challenges, and future directions.

Hepatocellular carcinoma (HCC) is a prevalent form of liver cancer that poses significant challenges regarding morbidity and mortality rates. In the context of HCC, immune cells play a vital role, especially concerning the presentation of antigens. This review explores the intricate interactions among immune cells within HCC, focusing on their functions in antigen presentation and the modulation of T-cell responses. We begin by summarizing the strategies that HCC uses to escape immune recognition, emphasizing the delicate equilibrium between immune surveillance and evasion. Next, we investigate the specific functions of various types of immune cells, including dendritic cells, natural killer (NK) cells, and CD8+ T cells, in the process of antigen presentation. We also examine the impact of immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the pathways involving programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), on antigen presentation, while taking into account the clinical significance of checkpoint inhibitors. The review further emphasizes the importance of immune-based therapies, including cancer vaccines and CAR-T cell therapy, in improving antigen presentation. In conclusion, we encapsulate the latest advancements in research, propose future avenues for exploration, and stress the importance of innovative technologies and customized treatment strategies. By thoroughly analyzing the interactions of immune cells throughout the antigen presentation process in HCC, this review provides an up-to-date perspective on the field, setting the stage for new therapeutic approaches.