Lung Cancer Microenvironment Research Articles

Methylation modification is a poor prognostic factor in non-small cell lung Cancer and regulates the tumor microenvironment: mRNA molecular structure and function

Non-small cell lung cancer (NSCLC) is the most common and deadly type of lung cancer, and its poor prognosis is closely related to the complex interactions of the tumor microenvironment. Through methylation analysis of tumor tissue samples from NSCLC patients, combined with high-throughput sequencing technology, the methylation status and structural characteristics of mRNA molecules were studied. Bioinformatics tools were used to analyze the regulatory effects of methylation modification on mRNA expression and genes associated with the tumor microenvironment. The results showed that the methylation level of specific mRNA was significantly correlated with the expression changes of tumor microenvironment-related factors. In addition, methylation modification affected mRNA stability and translation efficiency, further altering the metabolic activity and immune escape capacity of tumor cells. The results showed that mRNA with high methylation level was significantly associated with poor prognosis. Methylation modification profoundly affects the tumor microenvironment and prognosis of non-small cell lung cancer by altering the structure and function of mRNA molecules.

SLC40A1+ macrophages contribute to the immunosuppressive tumor microenvironment in EGFR-mutated lung cancer

SLC40A1+ macrophages contribute to the immunosuppressive tumor microenvironment in EGFR-mutated lung cancer

Characterizing dynamic tumor-immune interactions in lung adenocarcinoma through orthotopic allograft modeling.

The major clinical challenge in lung cancer immunotherapy is drug resistance. Therefore, establishing efficient orthotopic lung cancer mouse models to explore the mechanisms of drug immunotherapy resistance is highly important. In this study, we generated multiple fluorescently labeled lung adenocarcinoma cell lines from agenetically engineered KPZ mice model. Orthotopic transplantation of the primary 1F3 cell line induced a strong immune response, causing many small tumors to disappear, but some tumors evaded the immune attack and eventually formed large tumors. Tumor microenvironment analysis demonstrated that M2 macrophages play key roles in the immune response. Further mechanistic studies revealed that the chemokine CCL7 promoted the infiltration of M2 macrophages to facilitate immune escape, thereby promoting tumor growth in the orthotopic mouse model. Moreover, CCL7 levels were elevated in human lung cancer biopsies and positively correlated with M2 macrophage infiltration, and high CCL7 levels predicted advanced pathological stage and poor survival in lung cancer patients. Overall, we established a visualized and orthotopic mouse model with fluorescently labeled cells to better dissect the tumor microenvironment of lung cancer and define the critical role of CCL7 in promoting M2 macrophage polarization and tumorigenesis, providing new preclinical tools and potential targets for lung cancer immunotherapy.

Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors

BackgroundLung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients’ outcome.MethodsWe applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages. Focusing specifically on early stage samples, we validated our findings using an independent LUAD cohort with 70 bulk RNAseq and 15 scRNAseq datasets and on TCGA datasets.ResultsThrough our methodology and feature integration pipeline, we identified groups of immune cells related to disease stage as well as potential immune response or evasion and survival. More specifically, we reported a duality in the behavior of immune cells, notably natural killer (NK) cells, which was shown to be associated with survival and could be relevant for immune response or evasion. These distinct NK cell populations were further characterized using scRNAseq data, showing potential differences in their cytotoxic activity.ConclusionThe dual profile of several immune cells, most notably T-cell populations, have been discussed in the context of diseases such as cancer. Here, we report the duality of NK cells which should be taken into account in conjunction with other immune cell populations and behaviors in predicting prognosis, immune response or evasion.

Yi-Fei-San-Jie Chinese medicine formula reverses immune escape by regulating deoxycholic acid metabolism to inhibit TGR5/STAT3/PD-L1 axis in lung cancer

BackgroundYi-Fei-San-Jie Formula (YFSJF), a proprietary medicine of the First Affiliated Hospital of Guangzhou University of Chinese Medicine, has been widely used in clinical practice for several years and is currently being tested in randomized controlled trials for early-stage lung cancer in China. However, the mechanisms by which YFSJF affects lung cancer biology, particularly the immune microenvironment and metabolic processes, remain poorly understood. PurposeThis study aims to explore how YFSJF modulates the immune microenvironment and metabolism in lung cancer, specifically its unique role in inhibiting immune evasion by targeting the TGR5/STAT3/PD-L1 pathway, which has not previously been reported. MethodsComputed Tomography (CT) scan was used to assess YFSJF efficacy in patients with lung cancer and a mouse model of urethane-induced lung cancer. Histopathological evaluation, flow cytometry, and metabolomic analysis were used to assess lung tissue structure, immune cell subset changes, and metabolism modulation, respectively. Western blotting and immunohistochemistry were used to detect Ki67, TTF-1, TGR5, STAT3, p-STAT3, and PD-L1 protein expression. Serum cytokines were detected by ELISA. ResultsYFSJF effectively reduced the size of human lung cancer lesions and decreased the tumor burden and improved survival rates in mice. Lung tissue structure was also improved after YFSJF treatment. YFSJF regulated T-cell subsets, particularly by downregulating cells with PD-1-positive expression of CD3+, CD4+, and CD8+, and elevated serum TNF-α, IFN-γ, and GzmB levels. In addition, YFSJF modulated bile acid metabolism, particularly by inhibiting deoxycholic acid metabolism, which participates in immune regulation in lung cancer by acting on the G protein-coupled bile acid receptor TGR5. ConclusionFinally, YFSJF inhibited immune evasion by blocking the TGR5-mediated STAT3/PD-L1 pathway, weakening PD-L1 and PD-1 binding and reviving T-cell immune activity, thereby countering lung cancer immune evasion and exerting anti-tumor effects.

Sinensetin inhibits the movement ability and tumor immune microenvironment of non-small cell lung cancer through the inactivation of AKT/β-catenin axis.

Although current treatment strategies have improved clinical outcomes of non-small cell lung cancer (NSCLC) patients, side effect and prognosis remain a hindrance. Thus, safer and more effective therapeutical drugs are needed for NSCLC. Sinensetin (Sin) is a flavonoid from citrus fruits, which exhibits antitumor effect on diverse cancers. However, the effect and mechanism of Sin on NSCLC remain unknown. In this study, NSCLC cell lines, and tumor-bearing mice were treated with Sin. The effect and mechanism of Sin were addressed using cell counting kit-8, transwell, enzyme-linked immunosorbent assay, hematoxylin and eosin, immunohistochemistry, and western blot analysis assays in both cell and animal models. Sin reduced the cell viability of A549 and H1299, with the IC50 of 81.46 µM and 93.15 µM, respectively. Sin decreased invaded cell numbers, the expression of N-cadherin and vascular endothelial growth factor A (VEGFA), while increased the E-cadherin level, the cytotoxicity of CD8+ T cells, and the concentration of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α) in NSCLC cells. Mechanistically, Sin declined the expression of protein kinase B (AKT)/β-catenin pathway, which was restored with the application of SC79, an activator of AKT. The inhibitory role of Sin in NSCLC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and immune escape was reversed by the management of SC79. In vivo, Sin reduced tumor size and weight, and the expression of N-cadherin, VEGFA, and AKT/β-catenin pathway, but enhanced the level of E-cadherin and IFN-γ. Taken together, Sin suppressed cell growth, invasion, EMT and immune escape via AKT/β-catenin pathway in NSCLC.

Unveiling ficolins: diagnostic and prognostic biomarkers linked to the Tumor Microenvironment in Lung Cancer

BackgroundFicolins (FCNs) are a family of proteins, comprising FCN1, FCN2 and FCN3, and integral to the immune system which have been implicated in the onset and progression of tumors. Despite their recognized roles, a comprehensive analysis of FCNs in lung cancer remains elusive.MethodsWe employed a variety of bioinformatics tools, including UCSC, SangerBox, Ualcan, cBioPortal, String, Metascape, GeneMANIA, TIDE, CTD, and CAMP databases to investigate the differential expression, diagnostic and prognostic significance, genetic alterations, functional enrichment, immune infiltration, and potential immunotherapeutic implications of FCN1, FCN2, and FCN3 in lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD). Additionally, RT-qPCR and immunohistochemistry were utilized to validate the expressions of FCNs at the mRNA and protein levels in LUSC and LUAD.ResultsOur comprehensive bioinformatic analysis, supported by RT-qPCR and immunohistochemistry, revealed that the expressions of FCN1, FCN2 and FCN3 were consistently downregulated in both LUSC and LUAD tumor tissues. FCNs demonstrated significant diagnostic potential for LUSC and LUAD, with the area under the receiver operating characteristic curve (AUC) for FCN1 and FCN3 exceeding 0.90. Furthermore, FCN2 and FCN3 showed a strong negative correlation with overall survival (OS) in LUSC, whereas FCN1 and FCN2 were positively correlated with OS in LUAD, suggesting their prognostic value in lung cancer. Gene enrichment analysis indicated that FCNs were predominantly associated with the complement system and complement activation pathways. Immune infiltration analysis further revealed a significant positive correlation between FCNs and the presence of neutrophils and resting mast cells. Our analysis of immunotherapy outcomes revealed a significant disparity in the immunophenoscore (IPS) among lung cancer patients treated with immune checkpoint inhibitors (ICIs), distinguishing those with high FCN expression from those with low FCN expression. Additionally, we identified small molecule compounds related to FCNs and drugs pertinent to LUSC and LUAD.ConclusionFCNs held promise as diagnostic and prognostic biomarkers for LUSC and LUAD. This study also elucidated the relationship of FCNs with the tumor microenvironment, offering novel insights into the immunotherapeutic landscape for LUSC and LUAD.

Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer

Tumor-infiltrating lymphocytes (TILs) are essential components of the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Still, it is difficult to describe due to their heterogeneity. In this study, five cell markers from NSCLC patients were analyzed. We segmented tumor cells (TCs) and TILs using Efficientnet-B3 and explored their quantitative information and spatial distribution. After that, we simulated multiplex immunohistochemistry (mIHC) by overlapping continuous single chromogenic IHCs slices. As a result, the proportion and the density of programmed cell death-ligand 1 (PD-L1)-positive TCs were the highest in the core. CD8+ T cells were the closest to the tumor (median distance: 41.71 μm), while PD-1+T cells were the most distant (median distance: 62.2μm), and our study found that most lymphocytes clustered together within the peritumoral range of 10-30 μm where cross-talk with TCs could be achieved. We also found that the classification of TME could be achieved using CD8+ T-cell density, which is correlated with the prognosis of patients. In addition, we achieved single chromogenic IHC slices overlap based on CD4-stained IHC slices. We explored the number and spatial distribution of cells in heterogeneous TME of NSCLC patients and achieved TME classification. We also found a way to show the co-expression of multiple molecules economically.

Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.

Lung cancer remains a major global health threat due to its complex microenvironment, particularly the role of neutrophils, which are crucial for tumor development and immune evasion mechanisms. This study aimed to delve into the impact of lung cancer cell-conditioned media on neutrophil functions and their potential implications for lung cancer progression. Employing in vitro experimental models, this study has analyzed the effects of lung cancer cell-conditioned media on neutrophil IL-8 and IFN-γ secretion, apoptosis, PD-L1 expression, and T-cell proliferation by using techniques, such as ELISA, flow cytometry, immunofluorescence, and CFSE proliferation assay. The roles of IL-8/PD-L1 in regulating neutrophil functions were further explored using inhibitors for IL-8 and PD-L1. Lung cancer cell lines were found to secrete higher levels of IL-8 compared to normal lung epithelial cells. The conditioned media from lung cancer cells significantly reduced apoptosis in neutrophils, increased PD-L1 expression, and suppressed T-cell proliferation and IFN-γ secretion. These effects were partially reversed in the presence of IL-8 inhibitors in Tumor Tissue Culture Supernatants (TTCS), while being further enhanced by IL-8. Both apoptosis and PD-L1 expression in neutrophils demonstrated dose-dependency to TTCS. Additionally, CFSE proliferation assay results further confirmed the inhibitory effect of lung cancer cell-conditioned media on T-cell proliferation. This study has revealed lung cancer cell-conditioned media to modulate neutrophil functions through regulating factors, such as IL-8, thereby affecting immune regulation and tumor progression in the lung cancer microenvironment.

EPB.07 Choline Metabolism Reprogramming Mediates an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer

EPB.07 Choline Metabolism Reprogramming Mediates an Immunosuppressive Microenvironment in Non-Small Cell Lung Cancer

A single-cell RNA-seq dataset describing macrophages in NSCLC tumor and peritumor tissues

Examining tumor-associated macrophages in the immune microenvironment of non-small cell lung cancer (NSCLC) is essential for gaining an understanding of the genesis and development of NSCLC as well as for identifying key clinical therapeutic targets. Although previous studies have reported the diverse phenotypes and functions of macrophages in tumor tissues, thereby highlighting their significant role in the tumor microenvironment, the characteristic differences and correlations between tumor and peritumor tissue-derived macrophages that are necessary for an understanding of NSCLC progression remain unclear. Based on single-cell RNA sequencing, we generated a comprehensive dataset of transcriptomes from NSCLC tumor and peritumor tissues, thereby facilitating comprehensive analysis and providing significant insights. In summary, our dataset will serve as a valuable transcriptomic resource for further studies investigating NSCLC development.

P3.03J.04 Single-Cell Landscape of Senescent Cells in the Lung Cancer Microenvironment Unveils Pivotal Roles of Senescent Cancer Cells

P3.03J.04 Single-Cell Landscape of Senescent Cells in the Lung Cancer Microenvironment Unveils Pivotal Roles of Senescent Cancer Cells

AI drives the assessment of lung cancer microenvironment composition

PurposeThe abundance and distribution of tumor-infiltrating lymphocytes (TILs) as well as that of other components of the tumor microenvironment is of particular importance for predicting response to immunotherapy in lung cancer (LC). We describe here a pilot study employing artificial intelligence (AI) in the assessment of TILs and other cell populations, intending to reduce the inter- or intra-observer variability that commonly characterizes this evaluation. DesignWe developed a machine learning-based classifier to detect tumor, immune, and stromal cells on hematoxylin and eosin-stained sections, using the open-source framework QuPath. We evaluated the quantity of the aforementioned three cell populations among 37 LC whole slide images regions of interest, comparing the assessments made by five pathologists, both before and after using graphical predictions made by AI, for a total of 1110 quantitative measurements. ResultsOur findings indicate noteworthy variations in score distribution among pathologists and between individual pathologists and AI. The AI-guided pathologist's evaluations resulted in reduction of significant discrepancies across pathologists: three comparisons showed a loss of significance (p > 0.05), whereas other four showed a reduction in significance (p > 0.01). ConclusionsWe show that employing a machine learning approach in cell population quantification reduces inter- and intra-observer variability, improving reproducibility and facilitating its use in further validation studies.

Functions of CAFs in microenvironment of non-small cell lung cancer: based on updated hallmarks of cancer

Abstract Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, which ranks as the first malignant tumor in mortality. The occurrence and development of NSCLC are closely related to the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are considered to be critical regulators of the occurrence and development of NSCLC, which have essential effects on multiple biological characteristics of NSCLC. The hallmarks of cancer biology have been updated recently, however, there are no reviews revisiting the function of CAFs in tumor microenvironment. This article reviews the origin, markers, and classification of CAFs, their impacts on the characteristics of NSCLC, and potential therapeutic targets of CAFs to help develop individualized treatment plans for NSCLC.

1019P Bispecific PD1-IL2 antibody reshapes the inhibitory immune microenvironment of SMARCA4 mutant non-small cell lung cancer by reversing CD8+T cell exhaustion

1019P Bispecific PD1-IL2 antibody reshapes the inhibitory immune microenvironment of SMARCA4 mutant non-small cell lung cancer by reversing CD8+T cell exhaustion

Prognostic and predictive significance of soluble programmed death ligand 1 in bronchoalveolar lavage fluid in stage IV non-small cell lung cancer.

Patients with non-small cell lung cancer (NSCLC) have been shown to exhibit elevated levels of soluble programmed death-ligand 1 (sPD-L1) in the blood, associated with poor survival in NSCLC. The bronchoalveolar lavage fluid (BALF) composition reflects the tumor microenvironment of lung cancer. In this study, we investigated sPD-L1 levels in BALF and its role as a prognostic and predictive marker in patients with stage IV NSCLC. We prospectively obtained BALF from lung cancer patients who underwent bronchoscopy between January 2020 and September 2022 at Chungnam National University Hospital (CNUH). Finally, 94 NSCLC stage IV patients were included in this study. Soluble PD-L1 levels in BALF were measured using a human PD-L1 Quantikine ELISA kit. The correlation between PD-L1 expression in tumor cells and sPD-L1 in BALF was weakly positive (rho =0.314, P=0.002). The median overall survival (OS) of the low sPD-L1 in BALF group was 16.47 months [95% confidence interval (CI): 11.15-21.79 months], which is significantly longer than 8.87 months (95% CI: 0.0-19.88 months, P=0.001) in the high sPD-L1 in BALF group. In 64 patients treated with or without immune checkpoint inhibitors (ICIs), sPD-L1 in BALF was significantly associated with progression-free survival (PFS) and OS. In the subgroup analysis of 31 patients treated with ICI, the objective response rate (ORR) in the low sPD-L1 BALF group was significantly higher than in high sPD-L1 in BALF group (ORR: 60.9% vs. 12.5%, P=0.02). Soluble PD-L1 in BALF is a potential prognostic indicator for patients with stage IV NSCLC and a predictive marker for ICI treatment response.

Reprogramming hematopoietic stem cell metabolism in lung cancer: glycolysis, oxidative phosphorylation, and the role of 2-DG

Hematopoietic stem cells (HSCs) exhibit significant functional and metabolic alterations within the lung cancer microenvironment, contributing to tumor progression and immune evasion by increasing differentiation into myeloid-derived suppressor cells (MDSCs). Our aim is to analyze the metabolic transition of HSCs from glycolysis to oxidative phosphorylation (OXPHOS) in lung cancer and determine its effects on HSC functionality. Using a murine Lewis Lung Carcinoma lung cancer model, we conducted metabolic profiling of long-term and short-term HSCs, as well as multipotent progenitors, comparing their metabolic states in normal and cancer conditions. We measured glucose uptake using 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) and assessed levels of lactate, acetyl-coenzyme A, and ATP. Mitochondrial functionality was evaluated through flow cytometry, alongside the impact of the glucose metabolism inhibitor 2-DG on HSC differentiation and mitochondrial activity. HSCs under lung cancer conditions showed increased glucose uptake and lactate production, with an associated rise in OXPHOS activity, marking a metabolic shift. Treatment with 2-DG led to decreased T-HSCs and MDSCs and an increased red blood cell count, highlighting its potential to influence metabolic and differentiation pathways in HSCs. This study provides novel insights into the metabolic reprogramming of HSCs in lung cancer, emphasizing the critical shift from glycolysis to OXPHOS and its implications for the therapeutic targeting of cancer-related metabolic pathways.

The clinical significance of endoplasmic reticulum stress related genes in non-small cell lung cancer and analysis of single nucleotide polymorphism for CAV1.

In recent years, protein homeostasis imbalance caused by endoplasmic reticulum stress has become a major hallmark of cancer. Studies have shown that endoplasmic reticulum stress is closely related to the occurrence, development, and drug resistance of non-small cell lung cancer, however, the role of various endoplasmic reticulum stress-related genes in non-small cell lung cancer is still unclear. In this study, we established an endoplasmic reticulum stress scores based on the Cancer Genome Atlas for non-small cell lung cancer to reflect patient features and predict prognosis. Survival analysis showed significant differences in overall survival among non-small cell lung cancer patients with different endoplasmic reticulum stress scores. In addition, endoplasmic reticulum stress scores was significantly correlated with the clinical features of non-small cell lung cancer patients, and can be served as an independent prognostic indicator. A nomogram based on endoplasmic reticulum stress scores indicated a certain clinical net benefit, while ssGSEA analysis demonstrated that there was a certain immunosuppressive microenvironment in high endoplasmic reticulum stress scores. Gene Set Enrichment Analysis showed that scores was associated with cancer pathways and metabolism. Finally, weighted gene co-expression network analysis displayed that CAV1 was closely related to the occurrence of non-small cell lung cancer. Therefore, in order to further analyze the role of this gene, Chinese non-smoking females were selected as the research subjects to investigate the relationship between CAV1 rs3779514 and susceptibility and prognosis of non-small cell lung cancer. The results showed that the mutation of rs3779514 significantly reduced the risk of non-small cell lung cancer in Chinese non-smoking females, but no prognostic effect was found. In summary, we proposed an endoplasmic reticulum stress scores, which was an independent prognostic factor and indicated immune characteristics in the microenvironment of non-small cell lung cancer. We also validated the relationship between single nucleotide polymorphism locus of core genes and susceptibility to non-small cell lung cancer.

Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023.

Lung cancer (LC) is one of the most common malignant tumors in the world and the leading cause of cancer-related deaths, which seriously threatens human life and health as well as brings a heavy burden to the society. In recent years, the tumor microenvironment (TME) has become an emerging research field and hotspot affecting tumor pathogenesis and therapeutic approaches. However, to date, there has been no bibliometric analysis of lung cancer and the tumor microenvironment from 2014 to 2023.This study aims to comprehensively summarize the current situation and development trends in the field from a bibliometric perspective. The publications about lung cancer and the tumor microenvironment from 2014 to 2023 were extracted from the Web of Science Core Collection (WoSCC). The Microsoft Excel, Origin, R-bibliometrix, CiteSpace, and VOSviewer software are comprehensively used to scientifically analyze the data. Totally, 763 publications were identified in this study. A rapid increase in the number of publications was observed after 2018. More than 400 organizations published these publications in 36 countries or regions. China and the United States have significant influence in this field. Zhou, CC and Frontiers in Immunology are the most productive authors and journals respectively. Besides, the most frequently cited references were those on lung cancer pathogenesis, clinical trials, and treatment modalities. It suggests that novel lung cancer treatment models mainly based on the TME components, such as cancer-associated fibroblasts (CAFs) may lead to future research trends. The field of lung cancer and the tumor microenvironment research is still in the beginning stages. Gene expression, molecular pathways, therapeutic modalities, and novel detection technologies in this field have been widely studied by researchers. This is the first bibliometric study to comprehensively summarize the research trend and development regarding lung cancer and tumor microenvironment over the last decade. The result of our research provides the updated perspective for scholars to understand the key information and cutting-edge hotspots in this field, as well as to identify future research directions.