ArticleCancer medicine2021
HHLA2 deficiency inhibits non-small cell lung cancer progression and THP-1 macrophage M2 polarization.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- TREM2 mediates macrophage suppression of NLRP3 inflammasome pathway to promote non-small cell lung cancer progression.Molecular and cellular biochemistry · 2026Article
- Macrophages in lung cancer: principal factors, regulatory mechanisms, and therapeutic opportunities: a narrative review.Translational lung cancer research · 2026Review
- HHLA2 as an emerging immune checkpoint in lung cancer: linking EGFR signaling, macrophage polarization, and CD8Frontiers in immunology · 2026Review
- Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.Molecular and cellular biochemistry · 2026Review
- HHLA2 activates c-Met and identifies patients for targeted therapy in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Suppression of B7-H7 Enhanced MCF-7 Cancer Cell Line's Chemosensitivity to Paclitaxel.Molecular biotechnology · 2025Article
- Tumor-derived SEMA7A regulates fatty acid oxidation in the tumor-associated macrophages to promote the progression of non-small cell lung cancer.Frontiers in immunology · 2025Article
- Knockdown of HM13 Inhibits Metastasis, Proliferation, and M2 Macrophage Polarization of Non-small Cell Lung Cancer Cells by Suppressing the JAK2/STAT3 Signaling Pathway.Applied biochemistry and biotechnology · 2025Article
- Gold and Silver Nanoparticles Efficiently Modulate the Crosstalk Between Macrophages and Cancer Cells.International journal of nanomedicine · 2025Article
- Crosstalk between exosomes and tumor-associated macrophages in hepatocellular carcinoma: implication for cancer progression and therapy.Frontiers in immunology · 2025Review
- B7-H7 knockdown suppresses the proliferation, metastasis, and drug resistance of B-cell non-Hodgkin lymphoma cells by inhibiting the PI3K/Akt pathway.Frontiers in oncology · 2025Article
- LncRNA OIP5-AS1 suppresses lung adenocarcinoma progression and modulates macrophage polarization through the miR-429/DOCK4 regulatory axis.Frontiers in pharmacology · 2025Article
- Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- Exploring the immune landscape and drug prediction of an M2 tumor-associated macrophage-related gene signature in EGFR-negative lung adenocarcinoma.Thoracic cancer · 2024Article
- Article
- LINC00665 promotes the progression and immune evasion of lung cancer by facilitating the translation of TCF7 protein through dependence on IRES.Cancer cell international · 2024Article
- Review
- ALKBH5 modulates macrophages polarization in tumor microenvironment of ovarian cancer.Journal of ovarian research · 2024Article
- Review
- A CIC-related-epigenetic factors-based model associated with prediction, the tumor microenvironment and drug sensitivity in osteosarcoma.Scientific reports · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHuman endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a member of B7 family, which is upregulated in multiple tumors. However, its exact functions in non-small cell lung cancer (NSCLC) have not been fully understood. This study aimed to investigate the biological roles of HHLA2 in human NSCLC and the relevant mechanisms. In addition, the effects of tumor cell-derived HHLA2 on tumor-associated macrophage (TAM) polarization were explored.
methodsNSCLC cell growth, migration, and invasion were assessed by colony formation and modified Boyden chamber assays. Cell cycle and the CD163+ TAMs were examined by flow cytometry. A co-culture model of THP-1 macrophages and NSCLC cells was conducted to investigate the impacts of tumor cell-derived HHLA2 on THP-1 macrophage polarization. Moreover, a xenograft nude mouse model was established to explore the effects of HHLA2 on tumorigenesis in vivo.
resultsHHLA2 was upregulated in A549 and H1299 cells compared with the normal lung epithelial BEAS-2B cells. HHLA2 deficiency inhibited NSCLC cell proliferation, migration, invasion, and induced G0/G1 phase arrest partially via inhibiting EGFR/MAPK/ERK signaling pathway. Furthermore, HHLA2 knockdown inhibited M2 polarization of TAMs via downregulating IL-10. In addition, knockdown of HHLA2 inhibited tumor growth in vivo.
conclusionHHLA2 downregulation inhibited NSCLC growth and TAM M2 polarization. HHLA2 may serve as a therapeutic target and promising prognostic biomarker in NSCLC.
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