498 Downregulation of CD5 in CD8+ T tumour-infiltrating lymphocytes associates with increased level of activation and exhaustion
Notice bibliographique
Résumé
<h3>Background</h3> CD5, a member of the scavenger receptor cysteine-rich superfamily, is a marker for T cells and a subset of B cells (B1a). CD5 associates with T-cell and B-cell receptors and impair TCR signaling<sup>1 2</sup> and increased CD5 is an indication of B cell activation. Furthermore, CD5 levels on CD8+ T cell splenocytes were significantly increased after TCR/CD3 stimulation using ex vivo treatment with anti-CD3/anti-CD28 MAbs compared to non-stimulated CD8+ T splenocytes.<sup>3</sup> Previous studies have shown a correlation between CD5 and anti-tumour immunity where CD5 knockout mice inoculated with B16F10 melanoma cells had delayed tumour growth compared to wild type mice.<sup>4</sup> In tumour-infiltrating lymphocytes (TILs) isolated from lung cancer patients, CD5 levels were negatively correlated with anti-tumour activity and tumour-mediated activation-induced T cell death,<sup>5</sup> suggesting that CD5 could impair activation of anti-tumour T cells. However, the correlation between CD5 level expression and T cell activation and exhaustion in the tumour microenvironment and in peripheral organs is ill-defined and requires further investigation. <h3>Methods</h3> We determined CD5 levels in T cell subsets in different organs in mice bearing syngeneic 4T1 breast tumour homografts and assessed the relationship between CD5 and increased CD69 and PD-1 (markers of T cell activation and exhaustion) by flow cytometry. <h3>Results</h3> We report that T cell CD5 levels were higher in CD4+ T cells than in CD8+ T cells in 4T1 tumour-bearing mice, and that high CD5 levels on CD4+ T cells were maintained in peripheral organs (spleen and lymph nodes). However, both CD4+ and CD8+ T cells recruited to tumours had reduced CD5 compared to CD4+ and CD8+ T cells in peripheral organs. In addition, CD5highCD4+ T cells and CD5highCD8+ T cells from peripheral organs exhibited higher levels of activation and associated exhaustion compared to CD5lowCD4+ T cell and CD5lowCD8+ T cell from the same organs. Interestingly, CD8+ T cells among TILs and downregulated CD5 were activated to a higher level, with concomitantly increased exhaustion markers, than CD8+CD5+ TILs. <h3>Conclusions</h3> Thus, differential CD5 levels among T cells in tumours and lymphoid organs can be associated with different levels of T cell activation and exhaustion, suggesting that CD5 may be a therapeutic target for immunotherapeutic activation in cancer therapy. <h3>Acknowledgements</h3> The author thanks Rene Figueredo and Ronak Zareardalan for their assistance in animal work <h3>Ethics Approval</h3> This study was approved by the Animal Use Subcommittee of the University of Western Ontario <h3>References</h3> Azzam HS, et al., Fine tuning of TCR signaling by CD5. <i>The Journal of Immunology</i> 2001. 166(9): p. 5464–5472. Voisinne GA, Gonzalez de Peredo and Roncagalli R. CD5, an undercover regulator of TCR signaling. <i>Frontiers in Immunology</i> 2018;9:p. 2900. Alotaibi, F., et al., CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity. <i>European journal of immunology</i> 2020;50(5): p. 695–704. Tabbekh, M., et al., Rescue of tumor-infiltrating lymphocytes from activation-induced cell death enhances the antitumor CTL response in CD5-deficient mice. <i>The Journal of Immunology</i>, 2011. 187(1): p. 102–109. Dorothée, G., et al., In situ sensory adaptation of tumor-infiltrating T lymphocytes to peptide-MHC levels elicits strong antitumor reactivity. <i>The Journal of Immunology</i> 2005;174(11): p. 6888–6897.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».