Immune profiling of NF1-associated tumors reveals histologic subtype distinctions and heterogeneity: implications for immunotherapy
| Autor: | Ryan D. Roberts, Jonathan L. Finlay, Nancy Ratner, Timothy P. Cripe, Christopher R. Pierson, Kwangmin Choi, Nicholas D. Yeager, Michael Arnold, Kellie B. Haworth |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pathology medicine.medical_treatment Human leukocyte antigen Malignant transformation 03 medical and health sciences 0302 clinical medicine Immunophenotyping MPNST Internal medicine Medicine Neurofibromatosis Hematology business.industry FOXP3 Anatomical pathology Immunotherapy medicine.disease immunophenotype 3. Good health 030104 developmental biology Oncology NF1 030220 oncology & carcinogenesis neurofibromas immunotherapy business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.18301 |
| Popis: | // Kellie B. Haworth 1, 2 , Michael A. Arnold 3, 4 , Christopher R. Pierson 3, 4, 5 , Kwangmin Choi 6 , Nicholas D. Yeager 1 , Nancy Ratner 6 , Ryan D. Roberts 1, 2 , Jonathan L. Finlay 1 and Timothy P. Cripe 1, 2 1 Division of Hematology, Oncology, Blood and Marrow Transplant, Department of Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio, USA 2 Center for Childhood Cancer and Blood Diseases, The Research Institute, Nationwide Children’s Hospital, Columbus, Ohio, USA 3 Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA 4 Department of Pathology, The Ohio State University College of Medicine, Columbus, Ohio, USA 5 Division of Anatomy, Department of Biomedical Education and Anatomy, The Ohio State University College of Medicine, Columbus, Ohio, USA 6 Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA Correspondence to: Kellie B. Haworth, email: kellie.haworth@nationwidechildrens.org Keywords: NF1, MPNST, neurofibromas, immunotherapy, immunophenotype Received: December 14, 2016 Accepted: April 16, 2017 Published: May 30, 2017 ABSTRACT Successful treatment of neurofibromatosis type 1 (NF1)-associated tumors poses a significant clinical challenge. While the primary underlying genetic defect driving RAS signaling is well described, recent evidence suggests immune dysfunction contributes to tumor pathogenesis and malignant transformation. As immunologic characterizations, prognostic and predictive of immunotherapeutic clinical response in other cancers, are not fully described for benign and malignant NF1-related tumors, we sought to define their immunologic profiles. We determined the expression of human leukocyte antigen (HLA)-A/-B/-C, β-2-microglobulin (B2M), and T cell inhibitory ligands PD-L1 and CTLA-4 by microarray gene analysis and flow cytometry. We examined HLA-A/-B/-C, B2M, and PD-L1 expression on thirty-six NF1-associated tumor samples by immunohistochemistry, and correlated these with tumoral CD4 + , CD8 + , FOXP3 + , CD56 + , and CD45RO + lymphocytic infiltrates. We evaluated several tumors from a single patient, observing trends of increasing immunogenicity over time, even with disease progression. We observed similarly immunogenic profiles for malignant peripheral nerve sheath tumors (MPNST) and nodular and plexiform neurofibromas, contrasting with diffuse neurofibromas. These studies suggest that while immunotherapies may offer some benefit for MPNST and nodular and plexiform neurofibromas, tumor heterogeneity might pose a significant clinical challenge to this novel therapeutic approach. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|