The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation
Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the <i>NF1</i> tumor suppressor gene, which encodes the protein neu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/994 |
| _version_ | 1797264725196668928 |
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| author | Emily E. White Steven D. Rhodes |
| author_facet | Emily E. White Steven D. Rhodes |
| author_sort | Emily E. White |
| collection | DOAJ |
| description | Neurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the <i>NF1</i> tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss of <i>NF1</i> heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)—benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role of <i>NF1(Nf1)</i> haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role of <i>Nf1+/-</i> immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care. |
| first_indexed | 2024-04-25T00:33:28Z |
| format | Article |
| id | doaj.art-83ecb01eb4034d38bc13a1bae1ab9ce3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:28Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-83ecb01eb4034d38bc13a1bae1ab9ce32024-03-12T16:41:08ZengMDPI AGCancers2072-66942024-02-0116599410.3390/cancers16050994The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant TransformationEmily E. White0Steven D. Rhodes1Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USANeurofibromatosis type 1 (NF1) is a common genetic disorder resulting in the development of both benign and malignant tumors of the peripheral nervous system. NF1 is caused by germline pathogenic variants or deletions of the <i>NF1</i> tumor suppressor gene, which encodes the protein neurofibromin that functions as negative regulator of p21 RAS. Loss of <i>NF1</i> heterozygosity in Schwann cells (SCs), the cells of origin for these nerve sheath-derived tumors, leads to the formation of plexiform neurofibromas (PNF)—benign yet complex neoplasms involving multiple nerve fascicles and comprised of a myriad of infiltrating stromal and immune cells. PNF development and progression are shaped by dynamic interactions between SCs and immune cells, including mast cells, macrophages, and T cells. In this review, we explore the current state of the field and critical knowledge gaps regarding the role of <i>NF1(Nf1)</i> haploinsufficiency on immune cell function, as well as the putative impact of Schwann cell lineage states on immune cell recruitment and function within the tumor field. Furthermore, we review emerging evidence suggesting a dueling role of <i>Nf1+/-</i> immune cells along the neurofibroma to MPNST continuum, on one hand propitiating PNF initiation, while on the other, potentially impeding the malignant transformation of plexiform and atypical neurofibroma precursor lesions. Finally, we underscore the potential implications of these discoveries and advocate for further research directed at illuminating the contributions of various immune cells subsets in discrete stages of tumor initiation, progression, and malignant transformation to facilitate the discovery and translation of innovative diagnostic and therapeutic approaches to transform risk-adapted care.https://www.mdpi.com/2072-6694/16/5/994neurofibromatosis type 1 (NF1)plexiform neurofibromaatypical neurofibromamalignant peripheral nerve sheath tumorSchwann cellsimmune microenvironment |
| spellingShingle | Emily E. White Steven D. Rhodes The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation Cancers neurofibromatosis type 1 (NF1) plexiform neurofibroma atypical neurofibroma malignant peripheral nerve sheath tumor Schwann cells immune microenvironment |
| title | The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation |
| title_full | The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation |
| title_fullStr | The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation |
| title_full_unstemmed | The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation |
| title_short | The <i>NF1</i>+/- Immune Microenvironment: Dueling Roles in Neurofibroma Development and Malignant Transformation |
| title_sort | i nf1 i immune microenvironment dueling roles in neurofibroma development and malignant transformation |
| topic | neurofibromatosis type 1 (NF1) plexiform neurofibroma atypical neurofibroma malignant peripheral nerve sheath tumor Schwann cells immune microenvironment |
| url | https://www.mdpi.com/2072-6694/16/5/994 |
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