Titre
Identification de TCR tumeur- réactifs et antigène-spécifiques et suivi de leur dynamique chez des patients atteints de mélanome et traités par thérapie cellulaire
Type
mémoire de master/maîtrise/licence
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
AMREEIN, F.
Auteure/Auteur
Directrices/directeurs
HARARI, A.
Directeur⸱rice
DUTOIT, V.
Codirecteur⸱rice
Liens vers les personnes
Liens vers les unités
Faculté
Université de Lausanne, Faculté de biologie et médecine
Statut éditorial
Accepté
Date de publication
2023
Nombre de pages
41
Langue
français
Résumé
Purpose: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs), a type of cancer immunotherapy, has demonstrated promising results in patients with advanced cancer with cases of complete responses even after checkpoint blockade immunotherapy (CBI). However, only 40% of melanoma patients respond to ACT and the inconsistency of clinical response stresses the need for a finer understanding of the underlying mechanisms.
Experimental design: To understand the contribution of the antigenic or antitumoral reactivity, we interrogated cell products from two melanoma patients treated with TIL-ACT. Annotated clones were then tracked in longitudinal samples to understand the dynamics of tumor-reactive TILs. To this end, cell products were sequenced, screened with private peptides and interrogated against autologous tumors.
Results: The responder’s ACT product (ACTP) was enriched in tumor-reactive fraction, translating to a higher absolute number of tumor-reactive cells infused in this patient. Also, the number of recognized immunogenic epitopes was higher for this patient. Neoantigen-specific clones showed stronger responses than tumor-associated-antigen (TAA)-specific counterparts. The T-cell receptor (TCR) repertoire was highly influenced by the expansion phase of the ACTP. TILs persistence in the blood as well as tumor infiltration post TIL-ACT were more ambiguous in their dynamics, despite a trend for an association between clinical benefit and tumor-infiltration and blood persistence of identified tumor- reactive clonotypes.
Conclusion: In this small study, we could validate immune correlates of TIL-ACT efficacy with the characterization of ACT product specificity. The extensive study on the thirteen available patients would allow to deepen the knowledge on the dynamics of tumor-reactive and antigen-specific clonotypes, dissecting their blood persistence and tumor infiltration potential and association with clinical response.
Experimental design: To understand the contribution of the antigenic or antitumoral reactivity, we interrogated cell products from two melanoma patients treated with TIL-ACT. Annotated clones were then tracked in longitudinal samples to understand the dynamics of tumor-reactive TILs. To this end, cell products were sequenced, screened with private peptides and interrogated against autologous tumors.
Results: The responder’s ACT product (ACTP) was enriched in tumor-reactive fraction, translating to a higher absolute number of tumor-reactive cells infused in this patient. Also, the number of recognized immunogenic epitopes was higher for this patient. Neoantigen-specific clones showed stronger responses than tumor-associated-antigen (TAA)-specific counterparts. The T-cell receptor (TCR) repertoire was highly influenced by the expansion phase of the ACTP. TILs persistence in the blood as well as tumor infiltration post TIL-ACT were more ambiguous in their dynamics, despite a trend for an association between clinical benefit and tumor-infiltration and blood persistence of identified tumor- reactive clonotypes.
Conclusion: In this small study, we could validate immune correlates of TIL-ACT efficacy with the characterization of ACT product specificity. The extensive study on the thirteen available patients would allow to deepen the knowledge on the dynamics of tumor-reactive and antigen-specific clonotypes, dissecting their blood persistence and tumor infiltration potential and association with clinical response.
PID Serval
serval:BIB_C701DD844A9F
Date de création
2024-08-13T11:23:45.820Z
Date de création dans IRIS
2025-05-21T03:57:25Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
Mémoire no 10082 Mme Amrein.pdf
Version du manuscrit
imprimatur
Taille
3.23 MB
Format
Adobe PDF
PID Serval
serval:BIB_C701DD844A9F.P001
Somme de contrôle
(MD5):adeb288fddf7162037706d2f94093863