Leiden University Scholarly Publications

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Dopler-Zandavalle, A. (2025)

Not just a protein machine: how ribosomes regulate immune response

Doctoral Thesis
Ribosome specialization is an emerging field, and we slowly begin to grasp its impact on basic biological processes. While the common belief has been that ribosomes are passive mRNA-translating machines, recent literature has clearly demonstrated that this is not the case. This thesis summarizes the many flavors of ribosome specialization in cancer, and gives a detailed overview of the specific ribosomal proteins (RPs) involved in each process. Also, we uncover the differential roles RPs play in immune response against tumors, and how they work mechanistically. We found that changes to the ribosome regulate antigen presentation on tumor cells, which has a direct impact on the visibility of these tumor cells to our immune system. Together, the data presented in this thesis open many possible research directions and in the big picture, may yield a novel class of therapeutic strategies to overcome immunotherapy resistance, and to treat tumors using previously unknown strategies.
...Show moreRibosome specialization is an emerging field, and we slowly begin to grasp its impact on basic biological processes. While the common belief has been that ribosomes are passive mRNA-translating machines, recent literature has clearly demonstrated that this is not the case. This thesis summarizes the many flavors of ribosome specialization in cancer, and gives a detailed overview of the specific ribosomal proteins (RPs) involved in each process. Also, we uncover the differential roles RPs play in immune response against tumors, and how they work mechanistically. We found that changes to the ribosome regulate antigen presentation on tumor cells, which has a direct impact on the visibility of these tumor cells to our immune system. Together, the data presented in this thesis open many possible research directions and in the big picture, may yield a novel class of therapeutic strategies to overcome immunotherapy resistance, and to treat tumors using previously unknown strategies.
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mRNA translation
Ribosome specialization
Ribosomal proteins
T cell immunosurveillance
Antigen presentation
MHC class I
Cytokine response
All authors
Dopler-Zandavalle, A.
Supervisor
Schumacher, A.N.M.
Co-supervisor
Faller, W.J.
Committee
Neefjes, J.J.C.; Veen, A.G. van der; Tanenbaum, M.E.; Agami, R.; Wolkers, M.C.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2025-11-27
ISBN (print)
9789464964769

Funding

Sponsorship
The research described in this thesis was conducted at the Division of Oncogenomics and the Division Molecular Oncology and Immunology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL). This work was financially supported by the Dutch Research Council (NWO, OCENW-M20-373) and The Mark Foundation for Cancer.