TY - JOUR
T1 - The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score
AU - Parise, Ivy Zortéa S
AU - Parise, Guilherme A
AU - Noronha, Lúcia
AU - Surakhy, Mirvat
AU - Woiski, Thiago Demetrius
AU - Silva, Denise B
AU - Costa, Tatiana Ei-Jaick B
AU - Del-Valle, Maria Helena C P
AU - Komechen, Heloisa
AU - Rosati, Roberto
AU - Ribeiro, Melyssa Grignet
AU - Nascimento, Marilza Leal
AU - Souza, José Antônio de
AU - Andrade, Diancarlos P
AU - Paraizo, Mariana M
AU - Galvão, Marjorana Martini R
AU - Barbosa, José Renato S
AU - Barbosa, Miriam Lacerda
AU - Custódio, Gislaine C
AU - Figueiredo, Mirna M O
AU - Fabro, Ana Luiza M R
AU - Bond, Gareth
AU - Volante, Marco
AU - Lalli, Enzo
AU - Figueiredo, Bonald C
PY - 2019/11/5
Y1 - 2019/11/5
N2 - 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.
AB - 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.
U2 - 10.3390/cancers11111730
DO - 10.3390/cancers11111730
M3 - Article
C2 - 31694270
SN - 2072-6694
VL - 11
JO - Cancers
JF - Cancers
IS - 11
ER -