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Leukemic extracellular vesicles induce chimeric antigen receptor T cell dysfunction in chronic lymphocytic leukemia.
Cox, Michelle J; Lucien, Fabrice; Sakemura, Reona; Boysen, Justin C; Kim, Yohan; Horvei, Paulina; Manriquez Roman, Claudia; Hansen, Michael J; Tapper, Erin E; Siegler, Elizabeth L; Forsman, Cynthia; Crotts, Sydney B; Schick, Kendall J; Hefazi, Mehrdad; Ruff, Michael W; Can, Ismail; Adada, Mohamad; Bezerra, Evandro; Kankeu Fonkoua, Lionel Aurelien; Nevala, Wendy K; Braggio, Esteban; Ding, Wei; Parikh, Sameer A; Kay, Neil E; Kenderian, Saad S.
Afiliación
  • Cox MJ; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; University of Minnesota Graduate School, Bioinformatics and Computational Biology, Minneapolis, MN, USA.
  • Lucien F; Department of Urology, Mayo Clinic, Rochester, MN, USA.
  • Sakemura R; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Boysen JC; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Kim Y; Department of Urology, Mayo Clinic, Rochester, MN, USA.
  • Horvei P; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Department of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN, USA.
  • Manriquez Roman C; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
  • Hansen MJ; Department of Immunology, Mayo Clinic, Rochester, MN, USA.
  • Tapper EE; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Siegler EL; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Forsman C; T Cell Engineering, Mayo Clinic, Rochester, MN, USA.
  • Crotts SB; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA; Department of Immunology, Mayo Clinic, Rochester, MN, USA.
  • Schick KJ; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
  • Hefazi M; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Ruff MW; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
  • Can I; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
  • Adada M; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Bezerra E; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Kankeu Fonkoua LA; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Department of Oncology, Mayo Clinic, Rochester, MN, USA.
  • Nevala WK; Department of Immunology, Mayo Clinic, Rochester, MN, USA.
  • Braggio E; Department of Cancer Biology, Mayo Clinic, Phoenix, AZ, USA.
  • Ding W; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Parikh SA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
  • Kay NE; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Department of Immunology, Mayo Clinic, Rochester, MN, USA.
  • Kenderian SS; T Cell Engineering, Mayo Clinic, Rochester, MN, USA; Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA; Mayo Clinic Graduate School of Biomedical Sciences, Rochester, MN, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Immunology, Mayo Clinic, Roches
Mol Ther ; 29(4): 1529-1540, 2021 04 07.
Article en En | MEDLINE | ID: mdl-33388419
ABSTRACT
Chimeric antigen receptor (CAR) T cell therapy has yielded unprecedented outcomes in some patients with hematological malignancies; however, inhibition by the tumor microenvironment has prevented the broader success of CART cell therapy. We used chronic lymphocytic leukemia (CLL) as a model to investigate the interactions between the tumor microenvironment and CART cells. CLL is characterized by an immunosuppressive microenvironment, an abundance of systemic extracellular vesicles (EVs), and a relatively lower durable response rate to CART cell therapy. In this study, we characterized plasma EVs from untreated CLL patients and identified their leukemic cell origin. CLL-derived EVs were able to induce a state of CART cell dysfunction characterized by phenotypical, functional, and transcriptional changes of exhaustion. We demonstrate that, specifically, PD-L1+ CLL-derived EVs induce CART cell exhaustion. In conclusion, we identify an important mechanism of CART cell exhaustion induced by EVs from CLL patients.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Leucemia Linfocítica Crónica de Células B / Antígeno B7-H1 / Receptores Quiméricos de Antígenos Límite: Female / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Leucemia Linfocítica Crónica de Células B / Antígeno B7-H1 / Receptores Quiméricos de Antígenos Límite: Female / Humans / Male Idioma: En Revista: Mol Ther Asunto de la revista: BIOLOGIA MOLECULAR / TERAPEUTICA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos