Tumor-infiltrating T cells and PD-L1 expression in childhood malignant extracranial germ-cell tumors

Abstract

Although pediatric malignant extracranial germ-cell tumors (meGCTs) are among the most chemosensitive solid tumors, a group of patients relapse and die of disease. To identify new markers predicting clinical outcome, we examined the prognostic relevance of tumor-infiltrating T lymphocytes (TILs) and the expression of PD-1 and PD-L1 in a cohort of pediatric meGCTs by in situ immunohistochemistry. MeGCTs were variously infiltrated by T cell-subtypes according to the tumor subtype, tumor location and age at diagnosis. We distinguished three different phenotypes: i) tumors not infiltrated by T cells (immature teratomas and half of the yolk sac tumors), ii) tumors highly infiltrated by CD8 + T cells expressing PD-1, which identifies activated tumor-reactive T cells (seminomas and dysgerminomas), iii) tumors highly infiltrated by CD8 + T cells within an immunosuppressive tumor microenvironment characterized by CD4 + FOXP3 + Treg cells and PD-L1-expressing tumor cells (embryonal carcinomas, choriocarcinomas and the remaining yolk sac tumors). Tumor subtypes belonging mixed meGCTs were variously infiltrated, suggesting the coexistence of multiple immune microenvironments either facilitating or precluding the entry of T cells.These findings support the hypothesis that TILs influence the development of meGCTs and might be of clinical relevance to improve risk stratification and the treatment of pediatric patients. ARTICLE HISTORY

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

“…In pediatric patients with extracranial GCTs, high CD3+ T-cell infiltration, both in tumor nests and septa, indicated a favorable outcome [ 50 ]. Interestingly, PD-L1-positive TILs were reported only in single cases (one yolk sac tumor and three embryonal carcinomas).…”

“…), precludes any clear conclusions. The summary of the studies investigating the expression of PD-L1 in GCTs is presented in Table 6 [ 17 , 18 , 19 , 21 , 44 , 45 , 50 , 51 ].…”

Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes

“…The expression of PD-1 and PD-L1, along with the prognostic relevance of TIL, was also investigated in pediatric gonadal germ cell tumors, a heterogeneous group of tumors which represent 3–5% of all childhood cancers occurring before 15 years of age, and 15% of neoplasms in adolescents aged 15–19 years [ 111 ]. Three different cancer phenotypes were identified that were tumors (i) with no T cell infiltration, (ii) highly infiltrated by PD-1 + CD8 + T cells and (iii) highly infiltrated by CD8 + T cells within an immunosuppressive TME characterized by Treg cells and PD-L1 + neoplastic cells.…”

Seltene Erkrankungen der Mundhöhle, des Halses und des Pharynx

“…Alpha-fetoprotein (AFP) serves as posttherapeutic follow-up parameter 56 203 . The influence of immune checkpoint inhibitors on immature teratomas that are considered as “cold, deserted tumors” abandoned by the immune system 24 is currently unknown.…”

“…Bösartige unreife Tumore werden zusätzlich chemotherapeutisch behandelt, Alpha-Fetoprotein (AFP) dient als posttherapeutischer Verlaufsparameter 56 203 . Der Einfluss von Immuncheckpoint-Inhibitoren auf unreife Teratome, welche als „kalte, vom Immunsystem verlassene“ Tumore gelten 24 , ist bislang nicht geklärt.…”