PMID- 29137242
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221109
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 47
DP  - 2017 Oct 10
TI  - Immune profiling of NF1-associated tumors reveals histologic subtype distinctions 
      and heterogeneity: implications for immunotherapy.
PG  - 82037-82048
LID - 10.18632/oncotarget.18301 [doi]
AB  - 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, 
      beta-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.
FAU - Haworth, Kellie B
AU  - Haworth KB
AD  - Division of Hematology, Oncology, Blood and Marrow Transplant, Department of 
      Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Center for Childhood Cancer and Blood Diseases, The Research Institute, 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
FAU - Arnold, Michael A
AU  - Arnold MA
AD  - Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Pathology, The Ohio State University College of Medicine, Columbus, 
      Ohio, USA.
FAU - Pierson, Christopher R
AU  - Pierson CR
AD  - Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Department of Pathology, The Ohio State University College of Medicine, Columbus, 
      Ohio, USA.
AD  - Division of Anatomy, Department of Biomedical Education and Anatomy, The Ohio 
      State University College of Medicine, Columbus, Ohio, USA.
FAU - Choi, Kwangmin
AU  - Choi K
AD  - Division of Experimental Hematology and Cancer Biology, Cincinnati Children's 
      Hospital Medical Center, Cincinnati, Ohio, USA.
FAU - Yeager, Nicholas D
AU  - Yeager ND
AD  - Division of Hematology, Oncology, Blood and Marrow Transplant, Department of 
      Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
FAU - Ratner, Nancy
AU  - Ratner N
AD  - Division of Experimental Hematology and Cancer Biology, Cincinnati Children's 
      Hospital Medical Center, Cincinnati, Ohio, USA.
FAU - Roberts, Ryan D
AU  - Roberts RD
AD  - Division of Hematology, Oncology, Blood and Marrow Transplant, Department of 
      Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Center for Childhood Cancer and Blood Diseases, The Research Institute, 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
FAU - Finlay, Jonathan L
AU  - Finlay JL
AD  - Division of Hematology, Oncology, Blood and Marrow Transplant, Department of 
      Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
FAU - Cripe, Timothy P
AU  - Cripe TP
AD  - Division of Hematology, Oncology, Blood and Marrow Transplant, Department of 
      Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
AD  - Center for Childhood Cancer and Blood Diseases, The Research Institute, 
      Nationwide Children's Hospital, Columbus, Ohio, USA.
LA  - eng
GR  - K08 CA201638/CA/NCI NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R21 NS084885/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20170530
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5669868
OTO - NOTNLM
OT  - MPNST
OT  - NF1
OT  - immunophenotype
OT  - immunotherapy
OT  - neurofibromas
COIS- CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.
EDAT- 2017/11/16 06:00
MHDA- 2017/11/16 06:01
PMCR- 2017/10/10
CRDT- 2017/11/16 06:00
PHST- 2016/12/14 00:00 [received]
PHST- 2017/04/16 00:00 [accepted]
PHST- 2017/11/16 06:00 [entrez]
PHST- 2017/11/16 06:00 [pubmed]
PHST- 2017/11/16 06:01 [medline]
PHST- 2017/10/10 00:00 [pmc-release]
AID - 18301 [pii]
AID - 10.18632/oncotarget.18301 [doi]
PST - epublish
SO  - Oncotarget. 2017 May 30;8(47):82037-82048. doi: 10.18632/oncotarget.18301. 
      eCollection 2017 Oct 10.