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  • Governa, ValeriaLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups (author)

Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-02-25
  • Proceedings of the National Academy of Sciences (PNAS),2022
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-471022
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-471022URI
  • https://doi.org/10.1073/pnas.2114456119DOI
  • https://lup.lub.lu.se/record/ff9a1e6a-d69a-4d7b-b324-793e60cc2954URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Talbot, HugoLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups(Swepub:lu)hu5526ta (author)
  • Gonçalves de Oliveira, KelinLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)ke4436de (author)
  • Cerezo-Magaña, MyriamLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)med-mc_ (author)
  • Bång-Rudenstam, AnnaLund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Tumörmikromiljön,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Research Group Lung Cancer,Lund University Research Groups,Tumor microenvironment,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)an6188ba (author)
  • Johansson, Maria CLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-mjo (author)
  • Månsson, Ann-SofieLund University,Lunds universitet,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Lund University Research Groups(Swepub:lu)mikr-ama (author)
  • Forsberg Nilsson, Karin,1963-Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)karifors (author)
  • Marko-Varga, GyörgyLund University,Lunds universitet,Clinical Protein Science and Imaging,Forskargrupper vid Lunds universitet,Lund University Research Groups,Yonsei University,Tokyo Medical University(Swepub:lu)akem-gmv (author)
  • Enríquez Pérez, JulioLund University,Lunds universitet,Glioma immunterapigrupp,Forskargrupper vid Lunds universitet,Glioma immunotherapy group,Lund University Research Groups(Swepub:lu)med-jez (author)
  • Darabi, AnnaLund University,Lunds universitet,Glioma immunterapigrupp,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Glioma immunotherapy group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)wbl-ajo (author)
  • Malmström, JohanLund University,Lunds universitet,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,BioMS,Lund University Research Groups(Swepub:lu)medk-jma (author)
  • Bengzon, JohanLund University,Lunds universitet,Epilepsicentrum,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurokirurgi,Institutionen för kliniska vetenskaper, Lund,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Epilepsy Center,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Neurosurgery,Department of Clinical Sciences, Lund,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)neur-jbe (author)
  • Welinder, CharlotteLund University,Lunds universitet,BioMS,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-cbr (author)
  • Belting, MattiasUppsala University,Lund University,Lunds universitet,Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab,Lund Univ, Dept Clin Sci Lund, Sect Oncol, S-22185 Lund, Sweden.;Skane Univ Hosp, Dept Hematol Oncol & Radiophys, S-22185 Lund, Sweden.,Tumörmikromiljön,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Tumor microenvironment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)medk-mbe (author)
  • TumörmikromiljönForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences (PNAS)119:90027-84241091-6490

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