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

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          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.

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          Author and article information

          Journal
          Oncoimmunology
          Oncoimmunology
          KONI
          koni20
          Oncoimmunology
          Taylor & Francis
          2162-4011
          2162-402X
          2019
          13 December 2018
          : 8
          : 2
          Affiliations
          [a ] Department of Pathology, IRCCS, Ospedale Pediatrico Bambino Gesù , Rome, Italy
          [b ] Department of Oncohaematology, IRCCS, Ospedale Pediatrico Bambino Gesù , Rome, Italy
          [c ] Department of Biology, University of Pisa , Pisa, Italy
          [d ] Fondazione Bruno Kessler , Trento, Italy
          [e ] Department of Pathology, S.Orsola-Malpighi Hospital, University of Bologna , Bologna, Italy
          [f ] Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy
          [g ] Immunology Research Area IRCCS, Ospedale Pediatrico Bambino Gesù , Rome, Italy
          [h ] Department of Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori , Milan, Italy
          Author notes
          CONTACT Doriana Fruci doriana.fruci@ 123456opbg.net Immuno-Oncology Laboratory, Oncohaematology Department, Bambino Gesù Children’s Hospital, IRCCS , Viale di San Paolo 15, Rome 00146, Italy
          [*]

          These authors contributed equally to this work

          Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/koni.

          Article
          PMC6343784 PMC6343784 6343784 1542245
          10.1080/2162402X.2018.1542245
          6343784
          30713803
          9e3a3e7d-670e-46e6-a00e-8331bc2c5431
          © 2018 Taylor & Francis Group, LLC
          Page count
          Figures: 6, References: 48, Pages: 11
          Funding
          Funded by: Associazione Italiana per la Ricerca sul Cancro 10.13039/501100005010
          Award ID: 18495
          Funded by: Ministero della Salute (IT)
          Award ID: PE-2011-02351866
          This work was supported by the Associazione Italiana per la Ricerca sul Cancro [18495]; Ministero della Salute (IT) [PE-2011-02351866].
          Categories
          Original Research

          immunohistochemistry,PD-L1,PD-1,regulatory T cells,effector T cells,malignant extracranial germ-cell tumor,pediatric cancer,Tumor microenvironment

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