SCLC ICIs

BACKGROUND: The prognosis of small cell lung cancer (SCLC) patients is poor, and the standard first-line treatment for limited-stage small cell lung cancer (LS-SCLC) is still chemotherapy and thoracic radiotherapy. The primary objectives of our study were to confirm the superior efficacy of first-line immune checkpoint inhibitors (ICIs) plus etoposide and platinum (EP) for LS-SCLC and find crucial biomarkers. METHODS: We analyzed LS-SCLC patients from three medical centers, employing propensity score matching for group comparability...

BACKGROUND: Stereotactic body radiation therapy (SBRT) is often delivered in patients with oligometastatic disease (OMD). However, the specific subset of patients with polymetastatic non-small cell lung cancer (NSCLC) on novel systemic therapies who develop induced oligopersistant disease (OpersisD) or oligoprogressive disease (OprogD), as defined by the European Organisation for Research and Treatment of Cancer (EORTC) OMD classification, has not been well described. This study explores the outcomes of patients treated with this strategy...

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...

PURPOSE: Medications regulating immune homeostasis and gut microbiota could affect the efficacy of immune checkpoint inhibitors (ICIs). This study aimed to investigate the impact of concurrent medications on the clinical outcomes of patients with cancer receiving ICI therapy in South Korea. METHODS: We identified patients newly treated with ICI for non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and malignant melanoma (MM) between August 2017 and June 2020 from a nationwide database in Korea...

BACKGROUND: The application of immune checkpoint inhibitors (ICIs) in treating patients with extensive-stage small-cell lung cancer (ES-SCLC) has brought us new hope, but the real-world outcome is relatively lacking. Our aim was to investigate the clinical use, efficacy, and survival benefit of ICIs in ES-SCLC from real-world data analysis. METHODS: A retrospective analysis of ES-SCLC patients was conducted between 2012 and 2022. Progression-free survival (PFS) and overall survival (OS) were assessed between groups to evaluate the value of ICIs at different lines of treatment...

BACKGROUND: Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. METHODS: The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC...

Immune-related adverse events (IrAEs) involving the bladder are seldom reported and tend to be overlooked by oncologists. Cystitis caused by immune checkpoint inhibitors (ICIs) is rarely reported, with only four documented instances in the literature, of which just one case is attributed to pembrolizumab. We present a rare occurrence of pembrolizumab-induced hemorrhagic cystitis in a 71-year-old male with stage II-b lung adenocarcinoma with an chronic indwelling Foley catheter. He presented with persistent hematuria despite the completion of a course of antibiotics for a urinary infection; a cystoscopic examination was also normal...

Immune checkpoints inhibitors (ICIs) have markedly improved the therapeutic management of advanced NSCLC and, more recently, they have demonstrated efficacy also in the early-stage disease. Despite better survival outcomes with ICIs compared to standard chemotherapy, a large proportion of patients can derive limited clinical benefit from these agents. So far, few predictive biomarkers, including the programmed death-ligand 1 (PD-L1), have been introduced in clinical practice. Therefore, there is an urgent need to identify novel biomarkers to select patients for immunotherapy, to improve efficacy and avoid unnecessary toxicity...

Purpose: Lung cancer is a major cause of morbidity and mortality globally, necessitating the identification of predictive markers for effective immunotherapy. Mutations in SWI/SNF chromatin remodeling complex genes were reported sensitized human tumors to immune checkpoint inhibitors (ICIs), but the underlying mechanisms are unclear. This study aims to investigate the association between SWI/SNF gene ARID1B mutation and ICI response in non-small cell lung cancer (NSCLC) patients, to explore the functional consequences of ARID1B mutation on DNA damage response, immune microenvironment, and cGAS-STING pathway activation...

BACKGROUND: The advent of immune checkpoint inhibitors has dramatically changed the treatment paradigm for advanced non-small-cell lung cancer (NSCLC). Due to the complexity and diversity of stage III disease, the inclusion of immune checkpoint inhibitors (ICIs) in neoadjuvant treatment regimens is also required. However, immune-related adverse events (irAEs) limit the application of ICIs to a certain extent. Bronchopleural fistula (BPF) is a serious and fatal complication after pneumonectomy that is rarely reported, especially in patients who accept neoadjuvant immunotherapy or chemoimmunotherapy...

BACKGROUND: Immunotherapy has revolutionized cancer treatment. Recent studies have suggested that the efficacy of immunotherapy can be further enhanced by the influence of gut microbiota. In this study, we aimed to investigate the impact of bacteria on the effectiveness of cancer immunotherapy by combining analysis of clinical samples with validation in animal models. METHODS: In order to characterize the diversity and composition of microbiota and its relationship with response to immune checkpoint inhibitors (ICIs), 16S ribosomal RNA (rRNA) and GC-MS sequencing was performed on 71 stool samples from patients with advanced non-small cell lung cancer (NSCLC) prior to treatment with immune checkpoint blockade (ICB)...

BACKGROUND: Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+ )-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors...

BACKGROUND: For patients with EGFR/HER2 exon20 insertions, platinum-containing double-drug chemotherapy is still the standard treatment method. First-generation TKIs have almost no therapeutic activity against EGFR exon 20 insertions. The efficacy of second-and third-generation TKIs is still controversial. Immunotherapy research is scarce, and there is an urgent need for more evidence and new treatment options for this group of patients. METHODS: We reviewed patients with advanced NSCLC with EGFR/HER2 exon 20 insertion mutations treated in Shanghai Chest Hospital and Shanghai Pulmonary Hospital from 2015 to 2022 and assessed the efficacy of receiving chemotherapy, anti-angiogenic therapy and immunotherapy, including objective response rate (ORR) and disease control rate (DCR), and compared progression-free survival (PFS) and overall survival (OS)...

OBJECTIVE: Previous studies have shown that immune checkpoint inhibitors can improve the survival of patients with advanced non-small cell lung cancer with KRAS mutations; however, there is a lack of comparisons between treatment regimens associated with immune checkpoint inhibitors, and our study aims to compare several treatment parties to find a more effective treatment regimen. METHOD: A comprehensive literature search was conducted across multiple databases, namely PubMed, Web of Science, Embase, and Cochrane Library, to identify relevant studies...

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy...

Current evidence suggests that DEP domain containing 1 (DEPDC1) has an important effect on non-small-cell lung cancer (NSCLC). However, the diagnostic value and the regulatory function within NSCLC are largely unclear. This work utilized publicly available databases and in vitro experiments for exploring, DEPDC1 expression, clinical features, diagnostic significance and latent molecular mechanism within NSCLC. According to our results, DEPDC1 was remarkably upregulated in the tissues of NSCLC patients compared with non-carcinoma tissues, linked with gender, stage, T classification and N classification based on TCGA data and associated with smoking status and stage according to GEO datasets...

Small-cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all patients with SCLC are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation...

BACKGROUND: Immunotherapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC). However, a subset of the most advanced NSCLC patients fails to respond adequately to Immune checkpoint inhibitors (ICIs). Developing new nomograms and integrating prognostic factors are crucial for improving the clinical predictability of NSCLC patients undergoing ICIs. METHODS: Clinical information and genomic data of NSCLC patients undergoing ICIs were retrieved from cBioPortal...

BACKGROUND: Previous studies found that FAT1 was recurrently mutated and aberrantly expressed in multiple cancers, and the loss function of FAT1 promoted the formation of cancer-initiating cells in several cancers. However, in some types of cancer, FAT1 upregulation could lead to epithelial-mesenchymal transition (EMT). The role of FAT1 in cancer progression, which appears to be cancer-type-specific, is largely unknown. METHODS: QRT-PCR and immunochemistry were used to verify the expression of FAT1 in non-small cell lung cancer (NSCLC)...

Small cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICIs) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all SCLC patients are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation...