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

Governa, Valeria LU ; Talbot, Hugo LU ; Gonçalves de Oliveira, Kelin LU ; Cerezo-Magaña, Myriam LU orcid ; Bång-Rudenstam, Anna LU orcid ; Johansson, Maria C LU ; Månsson, Ann-Sofie LU ; Forsberg-Nilsson, Karin ; Marko-Varga, György LU and Enríquez Pérez, Julio LU orcid , et al. (2022) In Proceedings of the National Academy of Sciences of the United States of America 119(9). p.1-11
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glioma, Immunotherapy, Proteomics
in
Proceedings of the National Academy of Sciences of the United States of America
volume
119
issue
9
article number
e2114456119
pages
1 - 11
publisher
National Academy of Sciences
external identifiers
  • pmid:35217608
  • scopus:85125549020
  • pmid:35217608
ISSN
1091-6490
DOI
10.1073/pnas.2114456119
language
English
LU publication?
yes
additional info
Funding Information: We thank all the patients who contributed to this study and our colleagues at the Neurosurgery, Pathology, and Radiology departments (Lund University) for their important and continuous input. This work was supported by grants (to M.B.) from the Swedish Cancer Fund CAN 2017/664; the Swedish Research Council VR-MH 2018-02562; the European Union?s Horizon 2020 COFUND Programme: CanFaster 754299; the Swedish Childhood Cancer Foundation PR2020-0129; the Fru Berta Kamprad Foundation; the Sj?berg Foundation; the Sk?ne University Hospital donation funds; the governmental funding of clinical research within the national health services, ALF; and a generous donation by Viveca Jeppsson. Funding Information: ACKNOWLEDGMENTS. We thank all the patients who contributed to this study and our colleagues at the Neurosurgery, Pathology, and Radiology departments (Lund University) for their important and continuous input. This work was supported by grants (to M.B.) from the Swedish Cancer Fund CAN 2017/664; the Swedish Research Council VR-MH 2018-02562; the European Union’s Horizon 2020 COFUND Programme: CanFaster 754299; the Swedish Childhood Cancer Foundation PR2020-0129; the Fru Berta Kamprad Foundation; the Sjo€berg Foundation; the Skåne University Hospital donation funds; the governmental funding of clinical research within the national health services, ALF; and a generous donation by Viveca Jeppsson. Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.
id
ff9a1e6a-d69a-4d7b-b324-793e60cc2954
date added to LUP
2022-02-28 09:13:44
date last changed
2022-06-22 03:43:48
@article{ff9a1e6a-d69a-4d7b-b324-793e60cc2954,
  abstract     = {{<p>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.</p>}},
  author       = {{Governa, Valeria and Talbot, Hugo and Gonçalves de Oliveira, Kelin and Cerezo-Magaña, Myriam and Bång-Rudenstam, Anna and Johansson, Maria C and Månsson, Ann-Sofie and Forsberg-Nilsson, Karin and Marko-Varga, György and Enríquez Pérez, Julio and Darabi, Anna and Malmström, Johan and Bengzon, Johan and Welinder, Charlotte and Belting, Mattias}},
  issn         = {{1091-6490}},
  keywords     = {{Glioma; Immunotherapy; Proteomics}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{9}},
  pages        = {{1--11}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization}},
  url          = {{http://dx.doi.org/10.1073/pnas.2114456119}},
  doi          = {{10.1073/pnas.2114456119}},
  volume       = {{119}},
  year         = {{2022}},
}