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Single-cell derived tumor organoids display diversity in HLA class I peptide presentation
- Source :
- Nature Communications, Vol 11, Iss 1, Pp 1-10 (2020), Nature Communications, Nature Communications, 11(1). Nature Publishing Group
- Publication Year :
- 2020
- Publisher :
- Nature Publishing Group, 2020.
-
Abstract
- Tumor heterogeneity is a major cause of therapeutic resistance. Immunotherapy may exploit alternative vulnerabilities of drug-resistant cells, where tumor-specific human leukocyte antigen (HLA) peptide ligands are promising leads to invoke targeted anti-tumor responses. Here, we investigate the variability in HLA class I peptide presentation between different clonal cells of the same colorectal cancer patient, using an organoid system. While clone-specific differences in HLA peptide presentation were observed, broad inter-clone variability was even more prevalent (15–25%). By coupling organoid proteomics and HLA peptide ligandomics, we also found that tumor-specific ligands from DNA damage control and tumor suppressor source proteins were prominently presented by tumor cells, coinciding likely with the silencing of such cytoprotective functions. Collectively, these data illustrate the heterogeneous HLA peptide presentation landscape even within one individual, and hint that a multi-peptide vaccination approach against highly conserved tumor suppressors may be a viable option in patients with low tumor-mutational burden.<br />Immunotherapy may exploit alternative vulnerabilities of drug resistant cells. Here, the authors show that the HLA peptide presentation landscape is heterogeneous even within one individual, hinting that a multi-peptide vaccination approach against highly conserved tumor suppressors may be needed.
- Subjects :
- 0301 basic medicine
Proteome
Chemistry(all)
medicine.medical_treatment
Cell
Proteome/metabolism
General Physics and Astronomy
HLA Antigens/metabolism
TOR Serine-Threonine Kinases/metabolism
Proteomics
Ligands
Biochemistry
0302 clinical medicine
Single-cell analysis
HLA Antigens
Models
lcsh:Science
Antigen Presentation
Multidisciplinary
Tumor
Clone Cells/immunology
TOR Serine-Threonine Kinases
Neoplasm Proteins
3. Good health
Organoids
medicine.anatomical_structure
030220 oncology & carcinogenesis
Immunotherapy
Single-Cell Analysis
Colorectal Neoplasms
Signal Transduction
Colorectal Neoplasms/immunology
Tumour heterogeneity
Science
Antigen presentation
Human leukocyte antigen
Biology
Physics and Astronomy(all)
Models, Biological
Article
General Biochemistry, Genetics and Molecular Biology
Cell Line
03 medical and health sciences
Cell Line, Tumor
medicine
Organoid
Gene silencing
Humans
Neoplasm Proteins/metabolism
Biochemistry, Genetics and Molecular Biology(all)
General Chemistry
Biological
Clone Cells
030104 developmental biology
Cancer research
lcsh:Q
Organoids/immunology
Genetics and Molecular Biology(all)
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....70b44dcfe7d35bd9a39853a8fe316ef9