Peripheral blood tumor-infiltrating lymphocytes in a neuroblastoma model.

Autor:	Espinoza Vega ML; Servicio de Cirugía Pediátrica. Hospital Infantil Universitario Niño Jesús. Madrid., Luis Huertas AL; Servicio de Cirugía Pediátrica. Hospital Infantil Universitario Niño Jesús. Madrid., González Murillo A; Fundación de Investigación Biomédica. Hospital Infantil Universitario Niño Jesús. Madrid., Franco-Luzón L; Fundación de Investigación Biomédica. Hospital Infantil Universitario Niño Jesús. Madrid., Ramírez Orellana M; Servicio de Oncohematología, Unidad de Terapias Avanzadas. Hospital Infantil Universitario Niño Jesús. Madrid.
Jazyk:	English; Spanish; Castilian
Zdroj:	Cirugia pediatrica : organo oficial de la Sociedad Espanola de Cirugia Pediatrica [Cir Pediatr] 2020 Apr 01; Vol. 33 (2), pp. 84-90. Date of Electronic Publication: 2020 Apr 01.
Abstrakt:	Objective: To detect tumor-infiltrating lymphocytes (TILs) in the peripheral blood (PB) of a preclinical neuroblastoma model. Materials and Methods: Two types of preclinical models - immunodeficient mice and immunocompetent mice - were generated by injecting a cell suspension of neuroblastoma cell line NB36769 with MYCN gene (TH-MYCN+) overexpression. Spleen, tumor, and peripheral blood were studied using flow cytometry to detect PD-1+ T-cells. TCR-β immunosequencing was performed in matched samples (tumor and peripheral blood). Results: Most PB T-cells of immunodeficient mice were CD4 (control: 83.1%; tumor: 86.1%), with a small proportion of PD-1+ T-cells (control: 0.4%; tumor: 0.3%). However, the percentage of PD-1+ T-cells in the spleen was higher (control: 6.5%; tumor: 6.2%), and it was expressed in the CD4+ subset only. Regarding the TCR repertoire of immunocompetent mice, the proportion of the 10 most frequent sequences was significantly higher in tumors (11.09% ± 2.83%) than in the peripheral blood (1.59% ± 0.59%) (p=0.024). These findings are suggestive of clonotype enrichment within the tumor. 9 out of the 10 most frequent tumor clones were identified in the matched peripheral blood sample in 2 mice, and 6 out of 10 in one mouse. In addition, TILs with shared sequences from different animals were found. Conclusions: Our results in terms of immunophenotype and clonality suggest the presence of PB T-cells which could include TILs in a preclinical neuroblastoma model.
Databáze:	MEDLINE
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