| Title: |
Melanoma Clonal Heterogeneity Leads to Secondary Resistance after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes. |
| Authors: |
König, D.; Sandholzer, M.T.; Uzun, S.; Zingg, A.; Ritschard, R.; Thut, H.; Glatz, K.; Kappos, E.A.; Schaefer, D.J.; Kettelhack, C.; Passweg, J.R.; Holbro, A.; Baur, K.; Medinger, M.; Buser, A.; Lardinois, D.; Jeker, L.T.; Khanna, N.; Stenner, F.; Kasenda, B.; Homicsko, K.; Matter, M.; Rodrigues Mantuano, N.; Zippelius, A.; Läubli, H. |
| Publication Year: |
2024 |
| Collection: |
Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| Subject Terms: |
Humans; Lymphocytes; Tumor-Infiltrating/immunology; Tumor-Infiltrating/metabolism; Melanoma/therapy; Melanoma/immunology; Immunotherapy; Adoptive/methods; Male; Clone Cells; Female; Middle Aged; Skin Neoplasms/therapy; Skin Neoplasms/immunology; Skin Neoplasms/pathology |
| Description: |
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in patients with melanoma, although long-term responses seem restricted in patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. In this study, we describe a case of secondary resistance to TIL-ACT possibly due to intratumoral heterogeneity and selection of a resistant tumor cell clone by the transferred T cells. To the best our knowledge, this is the first case of clonal selection of a pre-existing nondominant tumor cell clone; this report demonstrates the mechanism involved in secondary resistance to TIL-ACT that can potentially change current clinical practice because it advocates for T-cell collection from multiple tumor sites and analysis of tumor heterogeneity before treatment with TIL-ACT. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2326-6074 |
| Relation: |
Cancer Immunology Research; https://iris.unil.ch/handle/iris/67297; serval:BIB_43CB67C6DE73 |
| DOI: |
10.1158/2326-6066.CIR-23-0757 |
| Availability: |
https://iris.unil.ch/handle/iris/67297; https://doi.org/10.1158/2326-6066.CIR-23-0757 |
| Accession Number: |
edsbas.FCBB32B9 |
| Database: |
BASE |