ArticleInternational journal of molecular sciences2023
Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Differential Expression and Co-Variation of HERV-Associated Transcripts, IL-17 Cytokines, and NFκB in Paired Colorectal Cancer Tissues.Biomedicines · 2026Article
- Cartilage Oligomeric Matrix Protein (COMP) Correlates with Disease Progression, Selected Immune Checkpoint Molecules and SIGLEC9 in Colorectal Cancer.International journal of molecular sciences · 2026Article
- The prognostic significance of B7-H3 expression in patients with advanced colorectal cancer.BMC cancer · 2026Article
- HHLA2 as an emerging immune checkpoint in lung cancer: linking EGFR signaling, macrophage polarization, and CD8Frontiers in immunology · 2026Review
- Poliovirus receptor (PVR) expression as a predictor of relapse in colorectal cancer: bioinformatics and virtual screening.Experimental biology and medicine (Maywood, N.J.) · 2026Article
- Recent advances and challenges in colorectal cancer: From molecular research to treatment.World journal of gastroenterology · 2025Review
- Immunotherapy in Gastrointestinal Cancers: Current Insights.Clinical pharmacology : advances and applications · 2025Review
- Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue.Current issues in molecular biology · 2024Article
- MicroRNA-486-3p affects cisplatin resistance in high-grade serous ovarian cancer by regulating TMIGD2: An experimental study.Heliyon · 2024Article
- HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway.World journal of surgical oncology · 2024Article
- Review
- Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies.ACS pharmacology & translational science · 2024Review
- Evaluation of HHLA2 and CD8 Immunohistochemical Expression in Colorectal Carcinoma and Their Prognostic Significance.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours.Cancers · 2023Article
- Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands.Therapeutic advances in vaccines and immunotherapy · 2023Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.
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