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

Author:

Governa Valeria1,Talbot Hugo1ORCID,Gonçalves de Oliveira Kelin1ORCID,Cerezo-Magaña Myriam1ORCID,Bång-Rudenstam Anna1ORCID,Johansson Maria C.1ORCID,Månsson Ann-Sofie1ORCID,Forsberg-Nilsson Karin2,Marko-Varga György345,Enríquez Pérez Julio6ORCID,Darabi Anna6ORCID,Malmström Johan7ORCID,Bengzon Johan68,Welinder Charlotte1ORCID,Belting Mattias129ORCID

Affiliation:

1. Department of Clinical Sciences Lund, Section of Oncology, Lund University, Lund 221 85, Sweden

2. Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Uppsala 751 85, Sweden

3. Clinical Protein Science and Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, Lund 221 85, Sweden

4. Chemical Genomics Global Research Lab, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea

5. First Department of Surgery, Tokyo Medical University, Tokyo 160-8402, Japan

6. Department of Clinical Sciences Lund, Section of Neurosurgery, Lund University, Lund 221 85, Sweden

7. Department of Clinical Sciences Lund, Division of Infection Medicine, Lund University, Lund 221 85, Sweden

8. Lund Stem Cell Center, Department of Clinical Sciences, Lund University, Lund 221 85, Sweden

9. Department of Hematology, Oncology, and Radiophysics, Skåne University Hospital, Lund 221 85, Sweden

Abstract

Significance Cancer immunotherapies, including checkpoint inhibitor blocking antibodies and antibody drug conjugates, currently revolutionize cancer treatment. However, a remaining challenge is the identification of tumor surfaceome (TS) targets for the design of more rational, individualized treatments. We have developed a procedure for unbiased mapping of TS targets in glioblastoma (GBM), i.e., the most common primary malignant brain tumor that remains among the most aggressive forms of cancer, and for which attempts to find effective treatments have failed so far. The present study provides additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification aimed at a better understanding of how to harness the TS for personalized immunotherapy.

Funder

The Swedish Cancer Society

The Swedish Research Council

The European Union''''s Horizon 2020 COFUND Programme; CanFaster

The Swedish Childhood Cancer Foundation

The Fru Berta Kamprad Foundation

The Sjoberg Foundation

The Skane University Hospital Donation Funds

The Governmental Funding of Clinical Research within the National Health Services, ALF

The Viveca Jeppsson Donation Fund

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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