The Prognostic Role of CD8+ T Lymphocytes in Childhood Adrenocortical Carcinomas Compared to Ki-67, PD-1, PD-L1, and the Weiss Score

Abstract

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.

Clinical prognostic factors in pediatric adrenocortical tumors: A meta‐analysis

“…Thirty‐six papers 2,5,16–18,20–47,49,50 allowed the evaluation of gender effect on outcome: females were found to have RR of 1.21, without reaching a significance ( P = .14; 95% CI 0.94‐1.55; I 2 0%).…”

Histopathological Analysis of Tumor Microenvironment and Angiogenesis in Pheochromocytoma

“…CD4 + T cells are helper T cells, stimulating CTLs activities (37). In addition, ACCs were also relatively frequently detected in childhood and increased TILs were reported in those young ACCs patients than adults (49). The most notable difference between ACCs and PHEOs was considered the effects of different hormones on TILs.…”

Cancer-testis Antigen FATE1 Expression in Adrenocortical Tumors Is Associated with A Pervasive Autoimmune Response and Is A Marker of Malignancy in Adult, but Not Children, ACC

“…However, recent studies showed that the immune response may have an important role in influencing the clinical course of patients with ACC. In pediatric ACC, MHC class II expression by tumor-infiltrating hematopoietic cells and the number of CD8 + T-lymphocytes are important prognostic indicators [13,20]. Even if in general only a small percentage of ACC tumor cells express PDL1, as detected by IHC [17,18], higher levels of PDL1 mRNA expression are significantly correlated with an inflammatory gene expression signature and longer DFS of adult patients with ACC [21].…”