Colorectal cancer patients-derived immunity-organoid platform unveils cancer-specific tissue markers associated with immunotherapy resistance Article Swipe
Annachiara Esposito
,
Antonio De Agostini
,
Giuseppe Quero
,
Geny Piro
,
Lorenzo Priori
,
Alessia Caggiano
,
Giulia Scaglione
,
Alessandra Battaglia
,
Maria Alessandra Calegari
,
Lisa Salvatore
,
Maria Bensi
,
MARIAGRAZIA MARATTA
,
Anna Ceccarelli
,
G. Trovato
,
Giannicola Genovese
,
Enrico Gurreri
,
Serena Ascrizzi
,
Maurizio Martini
,
Claudio Fiorillo
,
Andrea Fattorossi
,
Francesco De Sanctis
,
Stefano Ugel
,
Vincenzo Corbo
,
Sergio Alfieri
,
Giampaolo Tortora
,
Carmine Carbone
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1038/s41419-024-07266-5
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1038/s41419-024-07266-5
Colorectal cancer (CRC) is a devastating disease, ranking as the second leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors (ICIs) have emerged as promising treatments; however, their efficacy is largely restricted to a subgroup of microsatellite instable (MSI) CRCs. In contrast, microsatellite stable (MSS) CRCs, which account for the majority of cases, exhibit variable and generally weaker response to ICIs, with only a subset demonstrating exceptional responsiveness. Identifying novel cancer-specific tissue (CST) markers predictive of immunotherapy response is crucial for refining patient selection and overcoming treatment resistance. In this study, we developed clinically relevant CRC organoids and autologous immune system interaction platforms to model ICI response. We conducted a comprehensive molecular characterization of both responder and non-responder models, identifying CST markers that predict ICI response. Validation of these findings was performed using an independent cohort of patient specimens through multiplex immunofluorescence. Furthermore, we demonstrated that knocking out a key gene from the identified predictive signature in resistant organoids restored immune sensitivity and induced T-cell-mediated apoptosis. Overall, our results provide novel insights into the mechanisms underlying immunotherapy resistance and suggest new markers for enhancing patient selection. These findings may pave the way for new therapeutic options in MSS patients, potentially broadening the cohort of individuals eligible for immunotherapy.
Related Topics
Concepts
Immunotherapy
Colorectal cancer
Microsatellite instability
Cancer
Organoid
Medicine
Cancer immunotherapy
Multiplex
Immune system
Immunology
Oncology
Biology
Internal medicine
Bioinformatics
Gene
Microsatellite
Genetics
Allele
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1038/s41419-024-07266-5
- OA Status
- gold
- Cited By
- 10
- References
- 62
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4405003462
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4405003462Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1038/s41419-024-07266-5Digital Object Identifier
- Title
-
Colorectal cancer patients-derived immunity-organoid platform unveils cancer-specific tissue markers associated with immunotherapy resistanceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-12-04Full publication date if available
- Authors
-
Annachiara Esposito, Antonio De Agostini, Giuseppe Quero, Geny Piro, Lorenzo Priori, Alessia Caggiano, Giulia Scaglione, Alessandra Battaglia, Maria Alessandra Calegari, Lisa Salvatore, Maria Bensi, MARIAGRAZIA MARATTA, Anna Ceccarelli, G. Trovato, Giannicola Genovese, Enrico Gurreri, Serena Ascrizzi, Maurizio Martini, Claudio Fiorillo, Andrea Fattorossi, Francesco De Sanctis, Stefano Ugel, Vincenzo Corbo, Sergio Alfieri, Giampaolo Tortora, Carmine CarboneList of authors in order
- Landing page
-
https://doi.org/10.1038/s41419-024-07266-5Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1038/s41419-024-07266-5Direct OA link when available
- Concepts
-
Immunotherapy, Colorectal cancer, Microsatellite instability, Cancer, Organoid, Medicine, Cancer immunotherapy, Multiplex, Immune system, Immunology, Oncology, Biology, Internal medicine, Bioinformatics, Gene, Microsatellite, Genetics, AlleleTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
10Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 10Per-year citation counts (last 5 years)
- References (count)
-
62Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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