biostudies-literatureFerguson IDGabrielle's Angel Foundation for Cancer ResearchBLRD VAHoward Hughes Medical InstituteNINDS NIH HHSNCI NIH HHSNIGMS NIH HHS4121https://www.ebi.ac.uk/biostudies/studies/S-EPMC9287322biostudies-literatureUnknown13(1)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-Nature communicationsThe surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.PMC9287322R35 GM122451R35 GM118119P41 CA196276IK2 BX004183R01 CA226851R01 NS059690Lin YTMullins RDMartin TGShah NLopez-Girona ATuomivaara STTalbot APatino-Escobar BNix MAFerguson IDBesse LChoudhry PPrakash SWong SWHale MDriessen CWiita APKishishita APosey ADKasap CNieves Vasquez WNaik AVandenberg SLeung KKWolf JLMiao WEyquem JRamos EWells JAfalseThe surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.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 MUC1-2022-01-01T00:00:00Z2022 Jul2026-05-02T22:40:39.335Z2025-02-19T01:34:34.698ZS-EPMC92873223584057810.1038/s41467-022-31810-6