ArticleCancer immunology research2021
KIR3DL3 Is an Inhibitory Receptor for HHLA2 that Mediates an Alternative Immunoinhibitory Pathway to PD1.
Article in Cancer immunology research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Prognostic Value of HHLA2 in Patients with Solid Tumors: A Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Clinical Evaluation of HHLA2 in Hormone Receptor-Positive Breast Cancer: Expression Patterns and Prognostic Implications.Biomedicines · 2026Article
- Dynamics of Human Endogenous Retroviruses Expression, Proviral Load and Systemic Inflammatory Status Modulated by Physical Exercise and Aging.International journal of molecular sciences · 2026Article
- Lysine Targeting Group-Transfer Chimeras for Proximity Induction.Angewandte Chemie (International ed. in English) · 2026Article
- Deciphering the mechanistic landscape of immune checkpoint blockade in ccRCC: from molecular drivers to therapeutic responses.Frontiers in immunology · 2026Review
- Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.Molecular and cellular biochemistry · 2026Review
- Analysis of the profiles of human endogenous retroviruses W, K, and H and the systemic inflammatory status in vitiligo patients: insights on the dynamics of endogenous retroviral expression and its interplay with inflammatory response.Frontiers in cellular and infection microbiology · 2026Article
- HHLA2 as an emerging immune checkpoint in lung cancer: linking EGFR signaling, macrophage polarization, and CD8Frontiers in immunology · 2026Review
- Leveraging the heterogeneity of the NK cell repertoire for the development of immunotherapies for acute leukemia.Journal of translational medicine · 2025Review
- Unlocking new frontiers: novel immune targets for next-generation cancer immunotherapy.Korean journal of clinical oncology · 2025Review
- The Role of Human Endogenous Retroviruses in the Initiation and Progression of Melanoma.Biomedicines · 2025Review
- Optimization of Immunotherapy Strategies Based on Spatiotemporal Heterogeneity of Tumour-Associated Tissue-Resident Memory T Cells.Immunology · 2025Review
- Identification of esophageal cancer tumor antigens and immune subtypes for guiding vaccine development.Journal of thoracic disease · 2025Article
- Suppression of B7-H7 Enhanced MCF-7 Cancer Cell Line's Chemosensitivity to Paclitaxel.Molecular biotechnology · 2025Article
- Universal protection of allogeneic T-cell therapies from natural killer cells via CD300a agonism.Blood advances · 2025Article
- Circulating tumor-reactive KIRNature immunology · 2025Article
- Article
- Post-translational modification of NK cell receptors offers clues to antigenic specificity riddle.Frontiers in immunology · 2025Review
- HHLA2: a potential biomarker and therapeutic target in endocrine-related cancer.Endocrine oncology (Bristol, England) · 2025Review
- NK cells in renal cell carcinoma and its implications for CAR-NK therapy.Frontiers in cell and developmental biology · 2025Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Blockade of the PD1 pathway is a broadly effective cancer therapy, but additional immune-inhibitory pathways contribute to tumor immune evasion. HERV-H LTR-associating 2 (HHLA2; also known as B7H5 and B7H7) is a member of the B7 family of immunoregulatory ligands that mediates costimulatory effects through its interaction with the CD28 family member transmembrane and immunoglobulin domain containing 2 (TMIGD2). However, HHLA2 has also been known to have inhibitory effects on T cells. Here, we report that we have identified killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) as an inhibitory receptor for HHLA2 in T cells and natural killer (NK) cells and have generated HHLA2 and KIR3DL3 antibodies that block the immune-inhibitory activity of HHLA2, preserving the costimulatory signal. It is known that HHLA2 is frequently expressed in several tumor types, including clear cell renal cell carcinoma (ccRCC). We found that HHLA2 expression was nonoverlapping with PDL1 expression in ccRCC, suggesting that HHLA2 mediates a mechanism of tumor immune evasion that is independent from PDL1. Blockade of both the PD1 and KIR3DL3 pathways may be a more effective way to reverse tumor immune evasion.
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