Abstract
Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from 10 patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor CDR domain sequences, and mass spectrometry of 15 cNFs and the overlying skin was performed to study immune-related processes. Intratumoral T cells were detected in all cNFs. Tumors from individuals younger than the median age of the study participants (33 years), growing tumors, and tumors smaller than the data set median showed increased T cell density. Most samples displayed intratumoral or peritumoral aggregations of CD3-positive cells. T cell receptor sequencing demonstrated that the skin and cNFs host distinct T cell populations, whereas no dominant cNF-specific T cell clones were detected. Unique T cell clones were fewer in cNFs than in skin, and mass spectrometry suggested lower expression of proteins related to T cell-mediated immunity in cNFs than in skin. CD163-positive cells, suggestive of M2 macrophages, were abundant in cNFs. Human cNFs have substantial T cell and macrophage populations that may be tumor-specific.
| Original language | English |
|---|---|
| Article number | 100285 |
| Pages (from-to) | 100285 |
| Journal | Laboratory Investigation |
| Volume | 104 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2024 |
| MoE publication type | A1 Journal article-refereed |
Funding
Mass spectrometry analyses were performed at the Turku Proteomics Facility supported by Biocenter Finland. Immunohistochemistry services were obtained from the Histology core facility of the Institute of Biomedicine, University of Turku, Finland, and the Pathology Laboratory of Turku University Hospital, Turku, Finland. This study has been carried out in Turku University Hospital, which is a member of the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS). ERN GENTURIS is funded by the European Union. R.A.K. S.P. E.M. M.S. I.L. and J.P. conceptualized the study. R.A.K. S.P. K.L. E.M. M.J. P.R. and J.P. collected the samples and curated the data. R.A.K. S.P. K.L. E.M. M.J. E.F. I.L. and J.P. designed and performed the image analyses. P.H. and A.R. performed the mass spectrometry measurements. R.A.K. performed the statistical analyses. R.A.K. S.P. and J.P. acquired funding for the study. S.P. and J.P. supervised the study. R.A.K. S.P. and J.P. wrote the initial draft of the manuscript. All authors participated in the interpretation of the results, reviewed and edited the manuscript, and approved the final version of the manuscript. Immunohistochemistry data for CD3, CD4, CD8, FoxP3, CD68, and CD163 expressions in cNFs are available at https://doi.org/10.7303/syn51314057. The previously reported16 data set of immunolabeling for the mast cell marker CD117 is available at https://doi.org/10.7303/syn25613686. The T cell receptor sequencing data set is available at https://doi.org/10.7303/syn51315874. This publication was supported by a Subagreement from the Johns Hopkins University via the Neurofibromatosis Therapeutic Acceleration Program (NTAP) with funds provided by Grant Agreement form the Bloomberg Family Foundation. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Bloomberg Family Foundation or the Johns Hopkins University. The authors declare no conflicts of interest. The study adhered to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the Hospital District of Southwest Finland, and Turku University Hospital. All participants provided their written informed consent.
Keywords
- Humans
- Adult
- Neurofibromatosis 1/pathology
- Neurofibroma/metabolism
- Skin Neoplasms/metabolism
- Receptors, Antigen, T-Cell
- Tumor Microenvironment