The Prognostic Role of CD8 + T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score
- Creators
- Parise, Ivy Zortéa S.
- Parise, Guilherme
- Noronha, Lúcia
- Surakhy, Mirvat
- Woiski, Thiago
- Silva, Denise
- Costa, Tatiana Ei-Jaick
- Del-Valle, Maria Helena
- Komechen, Heloisa
- Rosati, Roberto
- Ribeiro, Melyssa
- Leal Nascimento, Marilza
- Antônio de Souza, José
- Andrade, Diancarlos
- Paraizo, Mariana
- Galvão, Marjorana Martini
- Barbosa, José Renato
- Lacerda Barbosa, Miriam
- Custódio, Gislaine
- Figueiredo, Mirna
- Fabro, Ana Luiza
- Bond, Gareth
- Volante, Marco
- Lalli, Enzo
- Figueiredo, Bonald
- Others:
- Pelé Pequeno Príncipe Research Institute [Curitiba, Brazil]
- Faculdades Pequeno Príncipe [Curitiba, Brazil]
- Hospital Infantil Joana Gusmão [Florianópolis, Brazil]
- Centro de Genética Molecular e Pesquisa do Câncer em Crianças [Curitiba, Brazil] (CEGEMPAC) ; Instituto de Pesquisa Pelé Pequeno Principe
- Serviço de Anatomia Patológica [Curitiba, Brazil] (Hospital de Clínicas) ; Universidade Federal do Paraná (UFPR)-Hospital de Clínicas [Curitiba, Brazil]
- Departamento de Medicina [Curitiba, Brazil] ; Pontifícia Universidade Católica do Paraná (PUCPR)
- Nuffield Department of Clinical Medicine [Oxford] ; University of Oxford [Oxford]
- Hospital Pequeno Príncipe [Curitiba, Brazil]
- Ciência Laboratório Médico Ltda [Florianópolis, Brazil] ; Hospital Infantil Joana de Gusmão [Florianópolis, Brazil]
- Department of Oncology [University of Turin] ; Università degli studi di Torino = University of Turin (UNITO)
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Departamento de Saúde Coletiva [Curitiba, Brazil] ; Federal University of Paraná [Curitiba, Brazil]
- This work was funded by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) Finance code 001, Conselho National de Desenvolvimento e Pesquisa (CNPq, Brazil), the Ludwig Institute for Cancer Research, and the CNRS EXPOGEN-CANCER. International Associated Laboratory (LIA).
Description
Adrenocortical carcinoma (ACC) is a rare disease among children. Our goal was to identify prognostic biomarkers in 48 primary ACCs from children (2.83 ± 2.3 y; mean age ± SD) by evaluating the tumor stage and outcome for an age of diagnosis before or after 3 years, and association with ACC cluster of differentiation 8 positive (CD8 +) cytotoxic T lymphocytes (CD8 +-CTL) and Ki-67 immunohistochemical expression (IHC). Programmed death 1(PD-1)/Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in ACC was analyzed in a second, partially overlapping cohort (N = 19) with a similar mean age. All patients and control children were carriers of the germline TP53 R337H mutation. Survival without recurrence for less than 3 years and death unrelated to disease were excluded. Higher counts of CD8 +-CTL were associated with patients diagnosed with ACC at a younger age and stage I, whereas a higher percentage of the Ki-67 labeling index (LI) and Weiss scores did not differentiate disease free survival (DFS) in children younger than 3 years old. No PD-1 staining was observed, whereas weakly PD-L1-positive immune cells were found in 4/19 (21%) of the ACC samples studied. A high CD8 +-CTL count in ACC of surviving children is compelling evidence of an immune response against the disease. A better understanding of the options for enhancement of targets for CD8 + T cell recognition may provide insights for future pre-clinical studies.
Abstract
International audience
Additional details
- URL
- https://www.hal.inserm.fr/inserm-02437545
- URN
- urn:oai:HAL:inserm-02437545v1
- Origin repository
- UNICA