Lung cancer, a major contributor to cancer-related fatalities worldwide, involves a complex pathogenesis. Cathepsins, lysosomal cysteine proteases, play roles in various physiological and pathological processes, including tumorigenesis. Observational studies have suggested an association between cathepsins and lung cancer. However, the causal link between the cathepsin family and lung cancer remains undetermined. This study employed Mendelian randomization analyses to investigate this causal association. The univariable Mendelian randomization analysis results indicate that elevated cathepsin H levels increase the overall risk of lung cancer, adenocarcinoma, and lung cancer among smokers. Conversely, reverse Mendelian randomization analyses suggest that squamous carcinoma may lead to increased cathepsin B levels. A multivariable analysis using nine cathepsins as covariates reveals that elevated cathepsin H levels lead to an increased overall risk of lung cancer, adenocarcinoma, and lung cancer in smokers. In conclusion, cathepsin H may serve as a marker for lung cancer, potentially inspiring directions in lung cancer diagnosis and treatment.

Though immune checkpoint blockade (ICB) against PD-1 has shown success in the treatment of lung cancer, not all patients respond. We have previously shown that adoptive transfer of double negative T (DNT) cells expanded from healthy donors can target leukemia but their role in treating established lung cancer is not clear. Here we explore the role of human DNT cells in targeting late-stage established lung cancer either alone or in combination with Nivolumab (anti-PD-1 antibody) and describe underlying mechanisms. DNT cells from resected lung cancer tissue of patients were analyzed by flow cytometry to determine their infiltration and PD-1 expression. Expansion capacity and anti-tumor function of lung cancer patient and healthy donor DNT cells were compared. Late-stage lung cancer xenograft models were developed to determine the anti-tumor effect of DNT cells alone or in combination with anti-PD-1 antibody, and the level of tumor-infiltrating DNT cells was quantified by histology and characterized by flow cytometry. Patient-derived tumor infiltrating lymphocytes contained a lower frequency of DNT cells with a higher expression of PD-1 relative to normal lung tissue. Ex vivo expanded patient- and healthy donor-derived DNT cells showed similar levels of cytotoxicity against lung cancer cells in vitro. Healthy donor-derived DNT cells significantly inhibited the growth of late-stage lung cancer xenografts, which was further augmented by anti-PD-1 through increased DNT cell tumor infiltration. This study supports the use of DNT cells for adoptive cellular therapy against lung cancer either alone or in combination with anti-PD-1.

Owing to its high mortality rate, lung cancer (LC) remains the most common cancer worldwide, with the highest malignancy diagnosis rate. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling (PAM) pathway is a critical intracellular pathway involved in various cellular functions and regulates numerous cellular processes, including growth, survival, proliferation, metabolism, apoptosis, invasion, and angiogenesis. This review aims to highlight preclinical and clinical studies focusing on the PAM signaling pathway in LC and underscore the potential of natural products targeting it. Additionally, this review synthesizes the existing literature and discusses combination therapy and future directions for LC treatment while acknowledging the ongoing challenges in the field. Continuous development of novel therapeutic agents, technologies, and precision medicine offers an increasingly optimistic outlook for the treatment of LC.

Aims: To elucidate the association between ferroptosis-related genes and prognosis in patients with lung adenocarcinoma (LUAD). Materials & methods: A ferroptosis-related gene signature was made by... Lay abstract Lung adenocarcinoma (LUAD) is a common type of lung cancer, a major contributor to cancer-related death in men and women worldwide. Ferroptosis is a form of regulated cell death that i...

Background: The pretreatment prognostic nutritional index (PNI) is an indicator of nutritional and immune status, and has potential use as a predictor of survival in cancer patients. Several retrospective studies have used the PNI to predict the outcome of lung cancer patients receiving different immune checkpoint inhibitors (ICIs), but the results have been inconsistent. The objective of our study is to assess the relationship of pretreatment PNI with survival outcomes in lung cancer patients who received ICI-based treatments by meta-analysis. Methods: We searched the EMBASE, PubMed, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology databases to identify studies that reported overall survival (OS) or progression-free survival (PFS) in eligible patients. Eight studies were eligible based on predefined inclusion and exclusion criteria. Data and pooled indicators were extracted from these studies. Meta-analysis was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and/or PFS and the prognostic value of pretreatment PNI. We completed the registration of the research protocol (Registration number: INPLASY202240087, DOI number: 10.37766/inplasy2022.4.0087). Results: We analyzed data from 8 eligible studies (831 patients). Meta-analysis showed that relative to patients with low pretreatment PNI, those with a high pretreatment PNI had better OS (HR = 2.50, 95% CI = 1.44–4.33, P = .001) and better PFS (HR = 1.94, 95% CI = 1.56–2.42, P < .001). Sensitivity analysis indicated these results were robust. There was also no evidence of publication bias. Conclusion: Lung cancer patients receiving ICI-based treatments who had higher pretreatment PNI had better OS and PFS.