ArticleCancer cell2023
The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity.
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Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68citing papers in PubMed
21.6field-weighted citation impact, top 1% of its field
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Who cites it
68 citing papers in PubMed, 85 citations in OpenAlex.
- TLR9 Agonists Potentiate Adoptive T-cell Therapy in Cancer through a B-cell-CD2 Costimulatory Axis.Cancer research · 2026Article
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- Patient‑specific profiling of TCR‑T cell efficacy enabled by a rapid and standardized reporter system.Protein & cell · 2026Article
- Genetic orchestration of the primary central nervous system lymphoma microenvironment.Biomarker research · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Oncogenic Mutations and Tumor Microenvironment Alterations in Diffuse Large B-Cell Lymphoma With Bulky Disease.Cancer medicine · 2026Article
- CMTM6 maintains B cell-intrinsic membrane CD40 stability to regulate anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Dynamic remodeling of the pancreas immune landscape in obesity.Nature communications · 2026Article
- Interpretable and scalable spatial gene set activity analysis with GESSO uncovers functional tissue architecture.bioRxiv : the preprint server for biology · 2026Article
- miR-133b induces antitumor immunity in cervical cancer through modulating CMTM6/PD-L1 axis.Molecular genetics and genomics : MGG · 2026Article
- Revealing the promising therapeutic targets and prognostic markers of primary mediastinal large B-cell lymphoma.Discover oncology · 2026Review
- Recent advances in the construction of humanized animal models and applications in translational medicine.Animal models and experimental medicine · 2026Review
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Single-Cell Profiling Reveals Distinct Immune Communication Networks in Centenarians and Elderly Controls.Aging cell · 2026Article
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans.EMBO reports · 2026Article
- Mutual Exclusion Analysis Shows that DUSP9 Negatively Regulates PD-L1 Expression and Acts as a Target to Enhance Anti-PD-1 Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- An expanded role for single-cell chemical genomics profiling in drug discovery.The Biochemical journal · 2026Review
- Dysfunctional decidual CD2Frontiers in immunology · 2026Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 10 institutions in 3 countries.
Patricia HoDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Johannes C MelmsDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Meri RogavaDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Chris J FrangiehDepartment of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Klarman Cell Observatory, the Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joanna PoźniakLaboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
Shivem B ShahDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Zachary WalshDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Oleksandr KyrysyukDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Amit Dipak AminDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Lindsay CaprioDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Benjamin T FullertonDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA.
Rajesh Kumar SoniProteomics and Macromolecular Crystallography Shared Resource, Columbia University, New York, NY 10032, USA.
Casey R AgerDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Jana BiermannDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Yiping WangDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Mohsen Khosravi-MaharlooeiColumbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259, USA.
Giorgia ZanettiColumbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Michael MuDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA.
Hijab FatimaDepartment of Pediatrics, Columbia University, New York, NY 10032, USA.
Emily K MooreColumbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Medicine, Division of Rheumatology, Columbia University, New York, NY 10032, USA.
Neil VasanDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Samuel F BakhoumDepartment of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Steven L ReinerDepartment of Pediatrics, Columbia University, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA.
Chantale BernatchezDepartment of Medical Oncology, MD Anderson Cancer Center, Houston, TX 77030, USA.
Megan SykesColumbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Microbiology and Immunology, Columbia University, New York, NY 10032, USA; Department of Surgery, Columbia University, New York, NY 10032, USA.
Emily M MaceDepartment of Pediatrics, Columbia University, New York, NY 10032, USA.
Kai W WucherpfennigDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Dirk SchadendorfDepartment of Dermatology, University Hospital Essen and German Cancer Consortium, Partner Site, 45147 Essen, Germany.
Oliver BechterDepartment of Oncology, KU Leuven, 3000 Leuven, Belgium.
Parin ShahDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA.
Gary K SchwartzDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA.
Jean-Christophe MarineLaboratory for Molecular Cancer Biology, Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
Benjamin IzarDepartment of Medicine, Division of Hematology and Oncology, Columbia University, New York, NY 10032, USA; Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY 10032, USA; Program for Mathematical Genomics, Department of Systems Biology, Columbia University, New York, NY 10032, USA; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA. Electronic address: bi2175@cumc.columbia.edu.
Columbia University Irving Medical Center · USColumbia University · USDana-Farber Cancer Institute · USVIB-KU Leuven Center for Cancer Biology · BEBroad Institute · USEssen University Hospital · DEKU Leuven · BEMayo Clinic in Arizona · USMemorial Sloan Kettering Cancer Center · USThe University of Texas MD Anderson Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MTumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MTranscriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2013 to 2026
$25.3MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007367 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI REINER, STEVEN L · 1985 to 2021
$25.1MMedical Scientist Training ProgramT32GM145440 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2022 to 2026
$7.3MTherapeutic Targeting of Immune Evasion from the MICA - NKG2D PathwayR01CA238039 · NCI · DANA-FARBER CANCER INST · PI Kai W Wucherpfennig · 2019 to 2026
$4.2MMechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6MStrategies to predict and overcome resistance to cancer immunotherapyR01CA279268 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2023 to 2026
$2.2MThe role of the CD58:CD2 axis in cancer immune evasion and resistance to immunotherapyR01CA266446 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FRANGIEH, CHRISTOPHER · 2022 to 2025
$2.0MDissecting mechanisms of immunotherapy resistance in melanoma patientsK08CA222663 · NCI · DANA-FARBER CANCER INST · PI IZAR, BENJAMIN · 2017 to 2021
$827kBD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600kDissecting drug resistance in serial uveal melanoma biopsies using integrated, multi-modal single-cell profiling and novel machine learning tools.R21CA263381 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IZAR, BENJAMIN · 2021 to 2022
$412kNCI NIH HHS K08 CA222663NCI NIH HHS P01 CA163222NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA238039NCI NIH HHS R01 CA266446NCI NIH HHS R01 CA279268NCI NIH HHS R21 CA263381NCI NIH HHS R37 CA258829NIGMS NIH HHS T32 GM007367NIGMS NIH HHS T32 GM145440NIH HHS S10 OD020056
Abstract
The cell-autonomous balance of immune-inhibitory and -stimulatory signals is a critical process in cancer immune evasion. Using patient-derived co-cultures, humanized mouse models, and single-cell RNA-sequencing of patient melanomas biopsied before and on immune checkpoint blockade, we find that intact cancer cell-intrinsic expression of CD58 and ligation to CD2 is required for anti-tumor immunity and is predictive of treatment response. Defects in this axis promote immune evasion through diminished T cell activation, impaired intratumoral T cell infiltration and proliferation, and concurrently increased PD-L1 protein stabilization. Through CRISPR-Cas9 and proteomics screens, we identify and validate CMTM6 as critical for CD58 stability and upregulation of PD-L1 upon CD58 loss. Competition between CD58 and PD-L1 for CMTM6 binding determines their rate of endosomal recycling over lysosomal degradation. Overall, we describe an underappreciated yet critical axis of cancer immunity and provide a molecular basis for how cancer cells balance immune inhibitory and stimulatory cues.
Indexed as
B7-H1 AntigenMelanomaAnimalsCD58 AntigensLymphocyte ActivationMiceT-LymphocytesB7-H1 AntigenCD58 Antigensbalance of co-inhibitory/co-stimulatorcancer immune evasioncancer immunologycancer immunotherapyCD2CD58CRISPR-Cas9 screenimmune checkpoint blockademass spec screenPDL1resistance to immune checkpoint blockadesingle-cell RNA-sequencing
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