999 Investigating the immunomodulatory role of innate lymphoid cells in epithelial ovarian carcinoma
Notice bibliographique
Résumé
Background Innate lymphoid cells (ILCs) are an emerging family of effector cells that mostly reside within non-lymphoid peripheral tissues and orchestrate innate and adaptive immunity in response to infections.1 ILCs play an important role in cancer including its ability to directly kill cancer cells and promote anti-tumour immunity within the tumour microenvironment (TME).2 In addition to these classical pro-inflammatory functions of ILCs, our group and others have identified a subset of immunoregulatory ILCs (ILCregs) in various diseases including cancer.3 We previously found a CD56+ ILCreg population that suppressed T cells in slow growing ex vivo tumour-infiltrating lymphocyte (TIL) cultures.4 The objective of this study is to identify markers that distinguish immunoregulatory and non-immunoregulatory ILCs straight from primary tumours and uncover its role within the TME of epithelial ovarian carcinoma (EOC). Methods Women with suspected EOC were recruited and consented pre-operatively at the Gynecology Cancer Clinic at Princess Margaret Hospital. Surgical resections were processed and analyzed by flow cytometry and single-cell RNA sequencing (scRNA-seq). In vitro stimulation of peripheral blood CD56+ ILCs were performed over 7 days in IL-15 with 50% ascites supernatant. Results We identified subsets of intratumoural ILCs including ILC1s, ILC2s, ILC3s, and CD56+ ILCs within lineage negative populations. Interestingly, a population of CD56+ GZMB- ILCs exhibited distinct tissue-resident-like properties including expression of tissue-retention marker CD69 and reduced expression of tissue-egress marker CD49e. Interestingly, transcriptomic profile of CD56+GZMB-CD49e- ILCs from our scRNA-seq dataset (n=3) had similar gene expression as intraepithelial ILC1s (ieILC1) from other studies.5 These ieILC1-like cells were associated with poor recurrent free survival and reduced granzyme B expression in CD8+ TILs. Moreover, ieILC1-like phenotypes can be induced from peripheral blood CD56+ cells using ascites supernatant from patients with EOC. Finally, ieILC1-like cells from primary tumours expressed gene signatures that have been previously upregulated in ILCregs and regulatory T cells (Tregs), suggesting that these populations may have immunoregulatory properties. Ongoing work is being done to identify whether ieILC1-like cells directly suppress T cells in vitro, and uncover mechanisms of immunosuppression. Conclusions Our findings suggest that ieILC1-like CD56+ cells are negatively associated with prognosis of EOC and may play a unique role in modulating the tumour microenvironment. Further investigation into the biology of ILCs in human tumours may provide novel therapeutic targets for ovarian carcinoma and beyond. References Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med 2015;21:698–708. Jacquelot N, Seillet C, Vivier E, Belz GT. Innate lymphoid cells and cancer. Nat Immunol. 2022; 23: 371–379. Chung DC, Jacquelot N, Ghaedi M, Warner K, Ohashi PS. Innate lymphoid cells: Role in immune regulation and cancer. Cancer. 2022; 14(9): 2071. Crome SQ, Nguyen LT, Lopez-Verges S, Yang SYCC, Martin B, Yam JY, Johnson DJ, Nie J, Pniak M, Yen PH, et al. A distinct innate lymphoid cell population regulates tumor-associated T cells. Nat Med 2017; 23: 368–375. Collins PL, Cella M, Porter SI, Li S, Gurewitz GL, Hong HS, Johnson P, Oltz EM, Colonna M. Gene regulatory programs conferring phenotypic identities to human NK cells. Cell. 2019;176: 348–360. Ethics Approval This study was conducted according to principles in the Declaration of Helsinki. The Research Ethics Board (REB) of the University Health Network (UHN) approved of this study. Fresh tissue was prepared from pre-operatively consented patients with EOC who were undergoing standard-of-care surgical procedures (UHN REB 10-0335).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».