Estrogen-related differences in antitumor immunity and the gut microbiome contribute to sexual dimorphism of colorectal cancer Article Swipe
Georgia Lattanzi
,
Federica Perillo
,
Angélica Díaz‐Basabe
,
Bruna Caridi
,
Chiara Amoroso
,
Alberto Baeri
,
Elisa Cirrincione
,
Michele Ghidini
,
Barbara Galassi
,
Elisa Cassinotti
,
Ludovica Baldari
,
Luigi Boni
,
Maurizio Vecchi
,
Flavio Caprioli
,
Federica Facciotti
,
Francesco Strati
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.17.576009
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1101/2024.01.17.576009
Colorectal cancer (CRC) is a multifaceted disease whose development and progression varies depending on tumor location, age of patients, infiltration of immune cells within cancer lesions, and the tumor microenvironment. These pathophysiological characteristics are additionally influenced by sex-related differences. The gut microbiome plays a pivotal role in the initiation and progression of CRC, and shapes anti-tumor immune responses but how the responsiveness of the immune system to the intestinal microbiota may contribute to the sexual dimorphism of CRC is largely unknown. Here, we studied survival, tumor-infiltrating immune cell populations and tumor-associated microbiome of a cohort of n=184 male and female CRC patients and functionally tested the immune system-microbiome interactions in in vivo and in vitro models of the disease. High-dimensional single-cell flow cytometry showed that female patients are enriched by tumor-infiltrating iNKT cells but depleted by cytotoxic T lymphocytes. The enrichment of oral pathobionts and a reduction of β-glucuronidase activity are distinctive traits characterizing the gut microbiome of women affected by CRC. Functional assays using a collection of human primary iNKT cell lines demonstrated that the gut microbiota of female patients functionally impairs iNKT cell anti-tumor functions interfering with the granzyme-perforin cytotoxic pathway. These results highlight a sex-dependent functional relationship between the gut microbiome, estrogen metabolism, and the decline of cytotoxic T cell responses, contributing to the sexual dimorphism observed in CRC patients with relevant implications for precision medicine and the design of targeted therapeutic approaches addressing sex bias in cancer.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2024.01.17.576009
- https://www.biorxiv.org/content/biorxiv/early/2024/01/20/2024.01.17.576009.full.pdf
- OA Status
- green
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4391050713
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4391050713Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2024.01.17.576009Digital Object Identifier
- Title
-
Estrogen-related differences in antitumor immunity and the gut microbiome contribute to sexual dimorphism of colorectal cancerWork title
- Type
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preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-01-20Full publication date if available
- Authors
-
Georgia Lattanzi, Federica Perillo, Angélica Díaz‐Basabe, Bruna Caridi, Chiara Amoroso, Alberto Baeri, Elisa Cirrincione, Michele Ghidini, Barbara Galassi, Elisa Cassinotti, Ludovica Baldari, Luigi Boni, Maurizio Vecchi, Flavio Caprioli, Federica Facciotti, Francesco StratiList of authors in order
- Landing page
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https://doi.org/10.1101/2024.01.17.576009Publisher landing page
- PDF URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/01/20/2024.01.17.576009.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.biorxiv.org/content/biorxiv/early/2024/01/20/2024.01.17.576009.full.pdfDirect OA link when available
- Concepts
-
Sexual dimorphism, Colorectal cancer, Gut microbiome, Estrogen, Microbiome, Biology, Immunity, Cancer, Internal medicine, Oncology, Medicine, Immunology, Bioinformatics, Genetics, Immune system, EndocrinologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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49Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.unknown. | 81 |
| abstract_inverted_index.cytometry | 123 |
| abstract_inverted_index.cytotoxic | 137, 192, 211 |
| abstract_inverted_index.depending | 13 |
| abstract_inverted_index.functions | 187 |
| abstract_inverted_index.highlight | 196 |
| abstract_inverted_index.location, | 16 |
| abstract_inverted_index.patients, | 19 |
| abstract_inverted_index.precision | 228 |
| abstract_inverted_index.reduction | 147 |
| abstract_inverted_index.responses | 58 |
| abstract_inverted_index.survival, | 85 |
| abstract_inverted_index.Colorectal | 1 |
| abstract_inverted_index.Functional | 163 |
| abstract_inverted_index.addressing | 237 |
| abstract_inverted_index.anti-tumor | 56, 186 |
| abstract_inverted_index.approaches | 236 |
| abstract_inverted_index.collection | 167 |
| abstract_inverted_index.contribute | 72 |
| abstract_inverted_index.dimorphism | 76, 219 |
| abstract_inverted_index.enrichment | 141 |
| abstract_inverted_index.functional | 199 |
| abstract_inverted_index.influenced | 36 |
| abstract_inverted_index.initiation | 49 |
| abstract_inverted_index.intestinal | 69 |
| abstract_inverted_index.microbiome | 42, 92, 157 |
| abstract_inverted_index.microbiota | 70, 178 |
| abstract_inverted_index.responses, | 214 |
| abstract_inverted_index.development | 9 |
| abstract_inverted_index.distinctive | 152 |
| abstract_inverted_index.interfering | 188 |
| abstract_inverted_index.metabolism, | 206 |
| abstract_inverted_index.microbiome, | 204 |
| abstract_inverted_index.pathobionts | 144 |
| abstract_inverted_index.populations | 89 |
| abstract_inverted_index.progression | 11, 51 |
| abstract_inverted_index.sex-related | 38 |
| abstract_inverted_index.single-cell | 121 |
| abstract_inverted_index.therapeutic | 235 |
| abstract_inverted_index.additionally | 35 |
| abstract_inverted_index.contributing | 215 |
| abstract_inverted_index.demonstrated | 174 |
| abstract_inverted_index.differences. | 39 |
| abstract_inverted_index.functionally | 104, 182 |
| abstract_inverted_index.implications | 226 |
| abstract_inverted_index.infiltration | 20 |
| abstract_inverted_index.interactions | 109 |
| abstract_inverted_index.lymphocytes. | 139 |
| abstract_inverted_index.multifaceted | 6 |
| abstract_inverted_index.relationship | 200 |
| abstract_inverted_index.sex-dependent | 198 |
| abstract_inverted_index.characterizing | 154 |
| abstract_inverted_index.responsiveness | 62 |
| abstract_inverted_index.characteristics | 33 |
| abstract_inverted_index.High-dimensional | 120 |
| abstract_inverted_index.tumor-associated | 91 |
| abstract_inverted_index.β-glucuronidase | 149 |
| abstract_inverted_index.granzyme-perforin | 191 |
| abstract_inverted_index.microenvironment. | 30 |
| abstract_inverted_index.system-microbiome | 108 |
| abstract_inverted_index.pathophysiological | 32 |
| abstract_inverted_index.tumor-infiltrating | 86, 131 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5037070826 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 16 |
| corresponding_institution_ids | https://openalex.org/I66752286 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7900000214576721 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.00933679 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |