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Publications

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Epublish 64 citations

PubMed: 35840578 DOI: 10.1038/s41467-022-31810-6

The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.

Nat Commun 13(1):4121

Authors: Ian D Ferguson, Bonell PatiƱo-Escobar, Sami T Tuomivaara, Yu-Hsiu T Lin, Matthew A Nix, Kevin K Leung, Corynn Kasap, Emilio Ramos, Wilson Nieves Vasquez, Alexis Talbot, Martina Hale, Akul Naik, Audrey Kishishita, Priya Choudhry, Antonia Lopez-Girona, Weili Miao, Sandy W Wong, Jeffrey L Wolf, Thomas G Martin, Nina Shah, Scott Vandenberg, Sonam Prakash, Lenka Besse, Christoph Driessen, Avery D Posey, R Dyche Mullins, Justin Eyquem, James A Wells, Arun P Wiita

Affiliations

  • Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, USA.
  • Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
  • Department of Medicine, Division of Hematology/Oncology, University of California, San Francisco, CA, USA.
  • Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA, USA.
  • INSERM U976, Institut de Recherche Saint Louis, UniversitĆ© de Paris, Paris, France.
  • Program in Chemistry and Chemical Biology, University of California, San Francisco, CA, USA.
  • Bristol Myers Squibb/Celgene, San Diego, CA, USA.
  • Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
  • Department of Pathology, University of California, San Francisco, CA, USA.
  • Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
  • Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
  • Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
  • Howard Hughes Medical Institute, San Francisco, CA, USA.
  • Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
  • Gladstone Institute for Genomic Immunology, San Francisco, CA, USA.
  • Department of Laboratory Medicine, University of California, San Francisco, CA, USA.

Abstract

The myeloma surface proteome (surfaceome) determines tumor interaction with the microenvironment and serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to define the myeloma surfaceome at baseline, in drug resistance, and in response to acute drug treatment. We provide a scoring system for surface antigens and identify CCR10 as a promising target in this disease expressed widely on malignant plasma cells. We engineer proof-of-principle chimeric antigen receptor (CAR) T-cells targeting CCR10 using its natural ligand CCL27. In myeloma models we identify proteins that could serve as markers of resistance to bortezomib and lenalidomide, including CD53, CD10, EVI2B, and CD33. We find that acute lenalidomide treatment increases activity of MUC1-targeting CAR-T cells through antigen upregulation. Finally, we develop a miniaturized surface proteomic protocol for profiling primary plasma cell samples with low inputs. These approaches and datasets may contribute to the biological, therapeutic, and diagnostic understanding of myeloma.

MeSH

Drug Resistance, Pharmaceutical Preparations, Therapeutics, Plasma Cells, Multiple Myeloma

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