pd-l1 and EGFR

Docetaxel +/- ramucirumab remains the standard-of-care therapy for patients with metastatic non-small-cell lung cancer (NSCLC) after progression on platinum doublets and immune checkpoint inhibitors (ICIs). The aim of our study was to investigate whether the cancer gene mutation status was associated with clinical benefits from docetaxel +/- ramucirumab. We also investigated whether platinum/taxane-based regimens offered a better clinical benefit in this patient population. A total of 454 patients were analyzed (docetaxel +/- ramucirumab n=381; platinum/taxane-based regimens n=73)...

Cell-surface proteins are important drug targets but historically have posed big challenges for the complete elimination of their functions. Herein, we report antibody-peptide conjugates (Ab-CMAs) in which a peptide targeting chaperone-mediated autophagy (CMA) was conjugated with commercially available monoclonal antibodies for specific cell-surface protein degradation by taking advantage of lysosomal degradation pathways. Unique features of Ab-CMAs including cell-surface receptor-/E3 ligase-independent degradation, feasibility towards different cell-surface proteins (e...

BACKGROUND: Programmed death ligand-1 (PD-L1) expression is a well-known predictive biomarker of response to immune checkpoint blockade in non-small cell lung cancer (NSCLC). However, there is limited evidence of the relationship between PD-L1 expression, clinicopathological features, and their association with major driver mutations in NSCLC patients in Latin America. METHODS: This retrospective study included patients from Argentina with advanced NSCLC, and centralized evaluation of PD-L1 expression concurrently with genomic alterations in the driver genes EGFR, ALK, ROS1, BRAF, and/or KRAS G12C in FFPE tissue samples...

BACKGROUND & AIMS: The programmed death-ligand 1 (PD-L1) is a major co-inhibitory checkpoint factor that controls T-cell activities in tumours. PD-L1 is expressed on immune cells and tumour cells. Whether tumour cell-expressed PD-L1 affects tumour cells in an immune cell-independent fashion remains largely elusive. In this study, we investigated the significance of tumour cell-expressed PD-L1 with a focus on downstream signals and changes in lipid metabolism. METHODS: Immune-independent functions of PD-L1 in tumour growth were investigated in vitro and in immuno-deficient mice in vivo ...

PURPOSE: Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions. METHODS: Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017)...

INTRODUCTION: Immunotherapy has been widely used in the treatment of various malignancies with satisfactory results. One of the agents for immunotherapy is an inhibitor of programmed cell death-1 and its ligands (PD-1 and PD-L1). However, attempts at utilizing PD-1/PD-L1 immunotherapy in osteosarcoma have not yielded favorable results. This may be due to differences in PD-L1 regulation and the immune landscape in osteosarcoma, as the mechanism is still poorly understood. Therefore, elucidating PD-L1 regulation in osteosarcoma is paramount in order to improve treatment results using immunotherapy...

BACKGROUND: STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC). PATIENTS AND METHODS: Surgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II trial (NCT00775385 IFCT-1801 TASTE trial) were examined...

BACKGROUND: Regional lymph node recurrence after radical surgery for non-small cell lung cancer (NSCLC) is an oligo-recurrent disease; however, no treatment strategy has been established. In the present study we aimed to determine the clinical outcomes of postoperative regional lymph node recurrence and identify prognostic predictors in the era of molecular-targeted therapy. METHODS: We retrospectively analyzed data on clinical characteristics and outcomes of patients with regional lymph node recurrence after surgery who underwent treatment for NSCLC between 2002 and 2022...

BACKGROUND: The anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immunotherapy has been extensively used in patients with non-small cell lung cancer (NSCLC) in which the tumors are negative for oncogenic alterations. However, whether PD-1/PD-L1 blockade therapy could be applicable in patients harboring oncogenic mutations is largely unknown. METHODS: In this retrospective study, we analyzed the safety and efficacy of anti-PD-1 inhibitor-based combinational therapy in a NSCLC cohort of 84 patients who harbored oncogenic alterations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), k-Ras, RET, HER2 and BRAF...

BACKGROUND: The study focuses on PD-L1 expression as an essential biomarker for gauging the response of EGFR/ALK wild-type NSCLC patients to FDA-approved immune checkpoint inhibitors (ICIs). It aims to explore clinical, molecular, and immune microenvironment characteristics associated with PD-L1 expression in EGFR/ALK wild-type lung adenocarcinoma patients eligible for ICI therapy. METHODS: In this retrospective study, tumor samples from 359 Chinese EGFR/ALK wild-type lung adenocarcinoma patients underwent comprehensive evaluations for PD-L1 expression and NGS-targeted sequencing...

Little is known about the relationship between programmed cell death-ligand 1 (PD-L1) expression and histologic and genetic features in real-world Chinese non-small cell lung cancer patients. From November 2017 to June 2019, tumor tissues were collected from 2674 non-small cell lung cancer patients. PD-L1 expression was detected with immunohistochemistry using the 22C3 and SP263 antibodies, and patients were stratified into subgroups based on a tumor proportion score of 1%, 1% to 49%, and ≥ 50%...

Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others...

Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC...

BACKGROUND AND OBJECTIVE: The management of resectable non-small cell lung cancer (NSCLC) has relied on surgery and adjuvant chemotherapy for the past two decades, but is now radically changing through the introduction of immunotherapy and targeted drugs. This review was conducted to summarize recent developments and highlight future directions. METHODS: A literature search for randomized phase 2/3 trials on the treatment of early-stage NSCLC was performed based on PubMed and the content on major oncology congresses during the last 3 years...

Background: Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) are two consecutive pathological processes that occur before invasive lung adenocarcinoma (LUAD). However, our understanding of the immune editing patterns during the progression of LUAD remains limited. Furthermore, we know very little about whether alterations in driver genes are involved in forming the tumor microenvironment (TME). Therefore, it is necessary to elucidate the regulatory role of TME in LUAD development from multiple dimensions, including immune cell infiltration, molecular mutation events, and oncogenic signaling pathways...

Despite advances in therapeutic strategies for colorectal cancer (CRC), CRC has a high disease incidence with significant morbidity and mortality worldwide. Notably, immunotherapy has shown limited efficacy in treating metastatic CRC, underscoring the need for alternative immunotherapeutic targets for the management of metastatic colorectal cancer (mCRC). In the present study, we evaluated the levels of the immune checkpoint proteins PD-L1, PD-L2 and B7-H3 in a large cohort retrospective study. We found that tumor B7-H3 (52...

BACKGROUND: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as 'super MPLC'. METHODS: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. FINDINGS: We report the genomic alteration landscape of super MPLC...

Lung cancer treatment has transitioned fully into the era of immunotherapy, yielding substantial improvements in survival rate for patients with advanced non-small cell lung cancer (NSCLC). In this report, we present a case featuring a rare epidermal growth factor receptor ( EGFR ) mutation accompanied by high programmed death-ligand 1 ( PD-L1 ) expression, demonstrating remarkable therapeutic efficacy through a combination of immunotherapy and chemotherapy. A 77-year-old male with no family history of cancer suffered from upper abdominal pain for more than half months in August 2020 and was diagnosed with stage IV (cT3N3M1c) lung squamous cell carcinoma (LUSC) harboring both a rare EGFR p...

BACKGROUND: The objective of this study was to explore the abilities of atezolizumab plus chemotherapy in preventing brain metastases (BMs) among metastatic non-small cell lung cancer (NSCLC) without initial BMs, as well as the risk factors of BMs. METHODS: Individual patient data from three trials involving first-line atezolizumab for metastatic NSCLC (IMpower130, IMpower131, and IMpower150) were pooled. Among patients without baseline BMs and without epidermal growth factor receptor (EGFR) and/or anaplastic lymphoma kinase (ALK) mutations, those receiving atezolizumab + chemotherapy ± bevacizumab were classified as the atezolizumab plus chemotherapy group and those receiving placebo + chemotherapy ± bevacizumab were classified as the chemotherapy group...

OBJECTIVE: Molecular subtyping of non-small cell lung cancer (NSCLC) is critical in the diagnostic evaluation of patients with advanced disease. This study aimed to examine whether samples from endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of intrathoracic lymph nodes and/or lung lesions are adequate for molecular analysis across various institutions. METHODS: We retrospectively reviewed all cases of linear EBUS-TBNA with a final bronchoscopic diagnosis of NSCLC entered in the Stather Canadian Outcomes registry for chest ProcEdures database...