PD-L1 Cancer

Lifileucel (AMTAGVI™), a one-time autologous T cell therapy derived and expanded from tumour-infiltrating lymphocytes (TIL) from a patient's own tumour, is being developed by Iovance Biotherapeutics, Inc. for the treatment of cancer. Lifileucel was granted accelerated approval based on objective response rate (ORR) in February 2024 in the USA for use in adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor...

BACKGROUND: The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC...

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers...

CONTEXT.—: Rapid advancements in the understanding and manipulation of tumor-immune interactions have led to the approval of immune therapies for patients with non-small cell lung cancer. Certain immune checkpoint inhibitor therapies require the use of companion diagnostics, but methodologic variability has led to uncertainty around test selection and implementation in practice. OBJECTIVE.—: To develop evidence-based guideline recommendations for the testing of immunotherapy/immunomodulatory biomarkers, including programmed death ligand-1 (PD-L1) and tumor mutation burden (TMB), in patients with lung cancer...

Identification of protein profiling on plasma exosomes by SERS can be a promising strategy for early cancer diagnosis. However, it is still challenging to detect multiple exosomal proteins simultaneously by SERS since the Raman signals of exosomes detected by conventional colloidal nanocrystals or two-dimensional SERS substrates are incomplete and complex. Herein, we develop a novel three-dimensional (3D) surround-enhancing SERS platform, named 3D se-SERS, for the multiplex detection of exosomal proteins. In this 3D se-SERS, proteins and exosomes are covered with "hotspots" generated by the gold nanoparticles, which surround the analytes densely and three-dimensionally, providing sensitive and comprehensive SERS signals...

BACKGROUND: Patients with extensive-stage small cell lung cancer (ES-SCLC) have an exceptionally poor prognosis and immune checkpoint inhibitors (ICIs) combined with etoposide-platinum is recommended as standard first-line therapy. However, which combination pattern is the best still remains unknown. This network meta-analysis was performed to compare the efficacy and safety of currently available patterns including an antiangiogenic agent containing regimen and probed into the most appropriate therapy for patients...

OBJECTIVES: Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. METHODS: We employed an RNA-sequencing cohort ( n  = 50) from Sun Yat-Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort ( n  = 244) from SYMH...

T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-β play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-β inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-β, termed AxF (scFv)2 , under the premise that combination with T cell redirecting strategies would improve clinical benefit...

BACKGROUND: Lung cancer is the leading cause of cancer death in Australia. Immunotherapy has improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC). Pembrolizumab is approved in first-line treatment as single-agent immunotherapy (SAI) or combination chemoimmunotherapy (CIT). In metastatic NSCLC programmed death-ligand 1 (PD-L1) ≥50% either regimen may be used. AIMS: We aim to identify patient and tumour characteristics that influence treatment selection...

BACKGROUND: Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models. METHODS: BA is a first-in-class bifunctional inhibitor of TGF-β and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models...

Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide and requires effective treatment strategies. Recently, the development of a novel multiple-target tyrosine kinase inhibitor, anlotinib, has drawn increasing attention, especially it shows advantages when combined with PD-1/PD-L1 blockade. However, the mechanism by which anlotinib improves immunotherapy and remodeling of the tumor microenvironment remains unclear. In this study, we found that anlotinib combined with PD-1 blockade significantly inhibited tumor growth and reduced tumor weight in a lung cancer xenograft model compared to any single treatment...

Simple and reliable profiling of tumor-derived exosomes (TDEs) holds significant promise for the early detection of cancer. Nonetheless, this remains challenging owing to the substantial heterogeneity and low concentration of TDEs. Herein, we devised an accurate and highly sensitive electrochemical sensing strategy for TDEs via simultaneously targeting exosomal mucin 1 (MUC1) and programmed cell death ligand 1 (PD-L1). This approach employs high-affinity aptamers as specific recognition elements, utilizes rolling circle amplification and DNA nanospheres as effective bridges and signal amplifiers, and leverages methylene blue (MB) and doxorubicin (DOX) as robust signal reporters...

The advent of immune checkpoint blockade therapy has revolutionized cancer treatments and is partly responsible for the significant decline in cancer-related mortality observed during the last decade. Immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1), have demonstrated remarkable clinical successes in a subset of cancer patients. However, a considerable proportion of patients remain refractory to immune checkpoint blockade, prompting the exploration of mechanisms of treatment resistance...

PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry...

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues...

Chemoradiotherapy (CRT) followed by consolidation of immune checkpoint inhibitors (ICIs), such as durvalumab or pembrolizumab, for patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression <1% remains a topic of controversy. Previous studies from PubMed, Cochrane Library and Embase databases were searched for a meta-analysis. A total of 16 studies were included in part one of the meta-analysis and it was observed that consolidation of ICIs after CRT improved overall survival (OS) [hazard ratio (HR) 1...

Serving as a pivotal immunotherapeutic approach against tumors, anti-PD-1/PD-L1 therapy amplifies the immune cells' capability to eliminate tumors by obstructing the interaction between PD-1 and PD-L1. Research indicates that immune checkpoint inhibitors are effective when a patient's gut harbors unique beneficial bacteria. As such, it has further been revealed that the gut microbiome influences tumor development and the efficacy of cancer treatments, with metabolites produced by the microbiome playing a regulatory role in the antitumor efficacy of Immune checkpoint inhibitors(ICBs)...

Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+ T cells...

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically changed the first-line treatment pattern of non-small cell lung cancer (NSCLC) without driver gene alterations. However, the optimal choice for second-line treatment after initial treatment with ICIs is unclear. This study aimed to clarify the efficacy and safety of ICI rechallenge therapy in locally advanced and advanced NSCLC. METHODS: We retrospectively analyzed the histories of 224 patients with locally advanced or advanced NSCLC treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy and/or antiangiogenic therapy in first-line treatment...

BACKGROUND: Breast cancer (BC/BRCA) is the most common carcinoma in women. The average 5-year survival rate of BC patients with stage IV disease is 26%. A considerable proportion of patients still do not receive effective therapy. It is an unmet need to identify novel biomarkers for BC patients. Herein, we evaluated whether the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) status is associated with the clinical outcomes of BC, based on data from The Cancer Genome Atlas (TCGA)...