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Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma.
Chiffelle, Johanna; Barras, David; Pétremand, Rémy; Orcurto, Angela; Bobisse, Sara; Arnaud, Marion; Auger, Aymeric; Rodrigo, Blanca Navarro; Ghisoni, Eleonora; Sauvage, Christophe; Saugy, Damien; Michel, Alexandra; Murgues, Baptiste; Fahr, Noémie; Imbimbo, Martina; Ochoa de Olza, Maria; Latifyan, Sofiya; Crespo, Isaac; Benedetti, Fabrizio; Genolet, Raphael; Queiroz, Lise; Schmidt, Julien; Homicsko, Krisztian; Zimmermann, Stefan; Michielin, Olivier; Bassani-Sternberg, Michal; Kandalaft, Lana E; Dafni, Urania; Corria-Osorio, Jesus; Trueb, Lionel; Dangaj Laniti, Denarda; Harari, Alexandre; Coukos, George.
Afiliación
  • Chiffelle J; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Barras D; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Pétremand R; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Orcurto A; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
  • Bobisse S; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Arnaud M; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Auger A; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Rodrigo BN; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, D
  • Ghisoni E; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, D
  • Sauvage C; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Saugy D; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Michel A; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Murgues B; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Fahr N; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Imbimbo M; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
  • Ochoa de Olza M; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
  • Latifyan S; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Medical Oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzer
  • Crespo I; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Benedetti F; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Genolet R; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Queiroz L; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Schmidt J; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital, Lausan
  • Homicsko K; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, D
  • Zimmermann S; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
  • Michielin O; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Medical Oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzer
  • Bassani-Sternberg M; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Kandalaft LE; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Center of Experimental The
  • Dafni U; Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece.
  • Corria-Osorio J; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Trueb L; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
  • Dangaj Laniti D; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland.
  • Harari A; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland. Electronic address: alexan
  • Coukos G; Ludwig Institute for Cancer Research, Lausanne Branch, Department of Oncology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Agora Cancer Research Center, Lausanne, Switzerland; Center for Cell Therapy, CHUV-Ludwig Institute, Lausanne, Switzerland; Immuno-oncology Service, D
Immunity ; 2024 Sep 10.
Article en En | MEDLINE | ID: mdl-39276771
ABSTRACT
Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8+ cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos