Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment.

SMARCA4, also known as transcription activator, is an ATP-dependent catalytic subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin-remodeling complexes that participates in the regulation of chromatin structure and gene expression by supplying energy. As a tumor suppressor that has aberrant expression in ∼10% of non-small-cell lung cancers (NSCLCs), SMARCA4 possesses many biological functions, including regulating gene expression, differentiation and transcription. Furthermore, NSCLC patients with SMARCA4 alterations have a weak response to conventional chemotherapy and poor prognosis. Therefore, the mechanisms of SMARCA4 in NSCLC development urgently need to be explored to identify novel biomarkers and precise therapeutic strategies for this subtype. This review systematically describes the biological functions of SMARCA4 and its role in NSCLC development, metastasis, functional epigenetics and potential therapeutic approaches for NSCLCs with SMARCA4 alterations. Additionally, this paper explores the relationship and regulatory mechanisms shared by SMARCA4 and its mutually exclusive catalytic subunit SMARCA2. We aim to provide innovative treatment strategies and improve clinical outcomes for NSCLC patients with SMARCA4 alterations.

Immunotherapy, remarkably immune checkpoint inhibitors (ICIs), has significantly altered the treatment landscape for non-small cell lung cancer (NSCLC). Despite their success, the discontinuation of ICIs therapy may occur due to factors such as prior treatment completion, disease progression during ICIs treatment, or immune-related adverse events (irAEs). As numerous studies highlight the dynamic nature of immune responses and the sustained benefits of ICIs, ICIs rechallenge has become an attractive and feasible option. However, the decision-making process for ICIs rechallenge in clinical settings is complicated by numerous uncertainties. This review systematically analyses existing clinical research evidence, classifying ICIs rechallenge into distinct clinical scenarios, exploring methods to overcome ICIs resistance in rechallenge instances, and identifying biomarkers to select patients likely to benefit from rechallenge. By integrating recent studies and new technologies, we offer crucial recommendations for future clinical trial design and provide a practical guideline to maximize the therapeutic benefits of immunotherapy for NSCLC patients.

Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

Background: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors’ primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected. Methods: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death. Results: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed. Conclusions: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer. Editor’s Perspective: What We Already Know about This Topic: What This Article Tells Us That Is New: