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    GENE:

    IL21R (Interleukin 21 Receptor)

    i
    Other names: IL21R, Interleukin 21 Receptor, CD360, Novel Interleukin Receptor, Interleukin-21 Receptor, IL-21 Receptor, NILR, CD360 Antigen, IL-21R, IMD56
    13d
    Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T cells in lymph nodes. (PubMed, Nat Immunol)
    The combination of Flt3L and anti-CTLA-4 enhanced therapeutic responses. Combination therapy is associated with the emergence of a CD8+ T cell subset characterized by the expression of Il21r and oligoclonal expansion of CD8+ T cells within tumors through a mechanism that is dependent on lymph node egress.
    Journal • IO biomarker
    |
    FLT3 (Fms-related tyrosine kinase 3) • CD8 (cluster of differentiation 8) • SLAMF6 (SLAM Family Member 6) • IL1R1 (Interleukin 1 receptor, type I) • IL21R (Interleukin 21 Receptor) • FLT3LG (Fms Related Receptor Tyrosine Kinase 3 Ligand)
    1m
    T-cell exhaustion indicator characterizes the tumor microenvironment landscape and predicts colon adenocarcinoma prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing. (PubMed, BMC Cancer)
    We proposed a non-invasive prediction method based on TEX-related genes, which effectively predicts survival outcomes and therapeutic responses in COAD patients. Additionally, FAT4 was found to regulate proliferative and apoptotic phenotypes in COAD.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • LAG3 (Lymphocyte Activating 3) • FAT4 (FAT Atypical Cadherin 4) • IL1R1 (Interleukin 1 receptor, type I) • IL21R (Interleukin 21 Receptor) • TNFSF14 (TNF Superfamily Member 14)
    11ms
    Identification of M1 macrophage infiltration-related genes for immunotherapy in Her2-positive breast cancer based on bioinformatics analysis and machine learning. (PubMed, Sci Rep)
    Lastly, we conducted immunohistochemistry staining to validate the aforementioned results. In conclusion, we found four M1 MIRGs that may be helpful for the diagnosis, prognosis, and immunotherapy of Her2-positive breast cancer.
    Journal • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • CCDC69 (Coiled-Coil Domain Containing 69) • FOXP3 (Forkhead Box P3) • IL1R1 (Interleukin 1 receptor, type I) • IL21R (Interleukin 21 Receptor)
    |
    HER-2 positive
    over1year
    Enhanced abscopal anti-tumor response via a triple combination of thermal ablation, IL-21, and PD-1 inhibition therapy. (PubMed, Cancer Immunol Immunother)
    Additionally, the combination of MWA, IL-21, and PD-1 mAbs demonstrated profound abscopal anti-tumor efficacy. Our findings provide support for further clinical investigation into a triple combination therapy involving MWA, IL-21, and ICIs for the treatment of metastatic cancer.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor)
    almost2years
    Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells. (PubMed, Mol Cancer)
    IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.
    Journal
    |
    CD8 (cluster of differentiation 8) • STAT1 (Signal Transducer And Activator Of Transcription 1) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor) • FOS (Fos Proto-Oncogene AP-1 Transcription Factor Subunit 2) • JUN (Jun proto-oncogene)
    |
    IL21R overexpression
    over2years
    MHC Class I and II Expression, Functional Tertiary Lymphoid Structure (TLS), and Outcomes in Early-Stage HER2-Positive (HER2+) Breast Cancer in NCCTG N9831 (Alliance) (SABCS 2023)
    A greater number of LA was associated with improved outcomes in pts with early-stage HER2+ breast cancer, particularly when treated with chemotherapy alone. Using histologic and genomic integration with the combination of pathological LA and TLS-related immune genes, we identified that pts with functional TLS with LA ≥ 1 and higher expression of BCL6 or IL21R had significantly improved outcomes when treated with trastuzumab. High MHC class I and II expressions are associated with the presence of functional TLS, underscoring the crucial role of antigen presentation in the generation of an effective adaptive immune response.
    PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • CD200 (CD200 Molecule) • ICOSLG (Inducible T Cell Costimulator Ligand) • TBX21 (T-Box Transcription Factor 21) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • IL1R1 (Interleukin 1 receptor, type I) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor)
    |
    HER-2 positive • HR negative
    |
    Herceptin (trastuzumab)
    almost3years
    MAST CELLS ARE MEDIATORS OF INFLAMMATORY EFFECTOR CELL RECRUITMENT AND FIBROSIS IN DERMAL CHRONIC GRAFT-VERSUS-HOST DISEASE (EHA 2023)
    Mast cells upon stimulation with IL33 were sources of many of these factors, production of which was blocked when treated with ibrutinib and ruxolitinib. Allogeneic wt recipients had significantly more cGVHD symptoms than mast cell-mcd B6.Cg-KitW-sh recipients. Clinical GVHD scores correlated with a significant increase in skin pathology (dermal thickness and sclerosis), collagen deposition, and expression of pro-fibrotic genes in WT as compared to mcd mice. Dermal mast cell numbers were increased in wt recipient mice, but were nearly undetectable in mcd recipient mice, implying that the mast cells that are present were recipient-derived and had survived conditioning.
    IO biomarker
    |
    IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • CXCL11 (C-X-C Motif Chemokine Ligand 11) • CCL2 (Chemokine (C-C motif) ligand 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • CXCR6 (C-X-C Motif Chemokine Receptor 6) • IL1B (Interleukin 1, beta) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • CXCL16 (C-X-C Motif Chemokine Ligand 16) • IL33 (Interleukin 33) • ST2 (Suppression Of Tumorigenicity)
    |
    Imbruvica (ibrutinib) • Jakafi (ruxolitinib)
    almost3years
    Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL (clinicaltrials.gov)
    P2, N=41, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2022 --> Dec 2023
    Trial primary completion date • Combination therapy
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL21R (Interleukin 21 Receptor)
    |
    Imbruvica (ibrutinib) • lenalidomide • Monjuvi (tafasitamab-cxix)
    over3years
    Expression of Interleukin-21 and Interleukin-21 receptor in lymphocytes derived from tumor-draining lymph nodes of breast cancer. (PubMed, Breast Dis)
    The higher intensity of IL-21 in CD4+T cells showed association with good prognosticators in breast cancer and warrants further investigation of the role played by IL-21 in immunity against breast cancer.
    Journal
    |
    CD19 (CD19 Molecule) • CD4 (CD4 Molecule) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor)
    |
    IL2 expression
    almost4years
    Functional tertiary lymphoid structure (TLS) and outcome in HER2-positive (HER2+) breast cancer in NCCTG N9831 (Alliance) (AACR 2022)
    Similar to sTIL, greater number of LA was associated with improved outcome in HER2+ pts treated with chemotherapy alone but not chemotherapy in combination with trastuzumab. Using histogenomic integration with the combination of pathological LA and TLS-related immune genes, we identified that pts with functional TLS with LA ≥ 1 and higher expression of BCL6 or IL21R had significantly improved outcome when treated with trastuzumab. Future studies are needed to further confirm these findings.Support: U10 CA180821, U24 CA196171, https://acknowledgments.alliancefound.org; Genentech;
    PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • IFNG (Interferon, gamma) • CD38 (CD38 Molecule) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • CD200 (CD200 Molecule) • TBX21 (T-Box Transcription Factor 21) • CXCR3 (C-X-C Motif Chemokine Receptor 3) • CXCR5 (C-X-C Motif Chemokine Receptor 5) • IL1R1 (Interleukin 1 receptor, type I) • IL21 (Interleukin 21) • IL21R (Interleukin 21 Receptor)
    |
    HER-2 positive
    |
    Herceptin (trastuzumab)
    almost4years
    Phase II MOR00208 in Combination With Lenalidomide for Patients With Relapsed or Refractory CLL, SLL or PLL or Older Patients With Untreated CLL, SLL or PLL (clinicaltrials.gov)
    P2, N=41, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
    Trial completion date • Trial primary completion date • Combination therapy
    |
    CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • IL21R (Interleukin 21 Receptor)
    |
    Imbruvica (ibrutinib) • lenalidomide • Monjuvi (tafasitamab-cxix)