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Background: The mechanisms involved in the malignant progression of lung adenocarcinoma (LUAD) are still inconclusive. Fibrinogen-like protein 1 ( FGL1 ) and LAG3 are a pair of immune checkpoints that create an inhibitory immune microenvironment in tumors. However, other roles of FGL1 in LUAD have not been extensively studied. Our study aims to explore the role of FGL1 in the malignant progression of LUAD and to provide new therapeutic targets and strategies for LUAD treatment., Methods: Differential gene expression of FGL1 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA), Oncomine, UALCAN, and Gene Expression Omnibus (GEO) databases. A pan-cancer analysis was conducted using the Oncomine, TIMER, and UALCAN databases. A total of 140 tumor tissues and paired normal tissues were collected, IHC and immunofluorescence staining were used to explore the expression of FGL1 . GeneMANIA database and STRING database were used to analyze gene-gene interaction and protein-protein interaction, respectively. A mutation analysis was conducted using the cBioPortal database, and an immune infiltration analysis was conducted using the TIMER database. A survival analysis was carried out using the GEPIA and PrognoScan database. The knockdown of FGL1 was confirmed by western blot (WB) and immunofluorescence staining. Cell proliferation was tested by cell cycle analysis and real-time cell analysis. RNA sequencing (RNA-seq) was used to explore the differential genes of FGL1 knockdown in LUAD cells., Results: Multiple databases showed that FGL1 was highly expressed in LUAD. The results of IHC indicated that FGL1 was highly expressed in the cytoplasm of LUAD cells. FGL1 was negatively associated with immune infiltration in LUAD. The main mutation of FGL1 is deep deletion, the altered group and high expression group indicated poor prognosis. The downregulation of FGL1 lead to a significantly decreased percentage of PC9 cells in S phase, but had little effect on the proliferation of Jurkat T cells. RNA-seq and GSEA analysis indicated that the differential genes were mainly enriched in MYC -target genes, which suggested that the downregulation of FGL1 inhibited cell proliferation by regulating MYC- target genes., Conclusions: FGL1 exerts in LUAD proliferation in addition to immune regulation. The downregulation of FGL1 inhibits the proliferation of LUAD cells by regulating MYC -target genes. Thus, FGL1 may be a novel therapeutic target in LUAD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-151/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Background: Primary tracheobronchial neoplasm is rare yet poses a serious threat to life. Due to its low incidence, the immune microenvironment of such tumors remained unclear. This study aimed to clarify the expression of programmed death-ligand 1 (PD-L1) and infiltration of immune cells in primary tracheobronchial neoplasm, which might be useful for guiding treatment and evaluating clinical outcome., Methods: We assessed retrospectively the expression of PD-L1 and infiltration in cells expressing CD8, CD16, CD68, CD163 and FOXP3 in 21 patients with primary tracheobronchial neoplasm who underwent surgery in Tangdu Hospital from January 2016 to July 2021. The expression of PD-L1 was assessed based on the tumor proportion score system. The density of immune cells was analyzed by automatic image analysis software., Results: In this study, all of 16 participants with adenoid cystic carcinoma (ACC) had no expression of PD-L1, whereas 4/5 (80%) of those with squamous cell carcinomas (SCC) were positive for PD-L1 expression. Compared with ACC, the density of FOXP3 + cells in both the intratumoral region and peritumoral region was higher in SCC (P<0.01). The density of FOXP3 + cells was significantly higher than that of CD8 + , CD16 + , and CD163 + cells in SCC in the intratumoral region (P<0.01). In contrast, the density of FOXP3 + cells was significantly lower than that of CD8 + , CD16 + , and CD68 + cells in ACC in both the intratumoral region and peritumoral regions. The density of CD68 + cells was significantly higher than that of CD8 + cells (P<0.05) and CD163 + cells (P<0.01) in ACC in the intratumoral region. Furthermore, the tumors of patients with metastasis more commonly of immune-excluded status, in which the CD8 + cells accumulated in peritumoral region., Conclusions: This study demonstrated that the expression of PD-L1 in primary tracheobronchial neoplasm was mainly concentrated in patients with SCC. In the immune microenvironment of SCC, FOXP3 + cells were the dominant immune cells, while in the immune microenvironment of ACC, CD68 + cells were the main immune cells. Therefore, the immune microenvironment was significantly different in primary tracheobronchial neoplasm according to histology., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-958). PH serves as an unpaid editorial board member of Translational Lung Cancer Research from March 2021 to February 2023. GM serves as an unpaid editorial board member of Translational Lung Cancer Research from August 2021 to July 2023. Dr. MT reports personal fees from MSD, Ono Pharmaceutical, Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical, and AstraZeneca KK. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)