TCR Pathway Mutations in Mature T Cell Lymphomas.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 11 2023
15 11 2023
Historique:
received:
12
09
2022
accepted:
06
06
2023
pmc-release:
15
05
2024
medline:
8
11
2023
pubmed:
6
11
2023
entrez:
6
11
2023
Statut:
ppublish
Résumé
Mature T cell lymphomas are heterogeneous neoplasms that are aggressive and resistant to treatment. Many of these cancers retain immunological properties of their cell of origin. They express cytokines, cytotoxic enzymes, and cell surface ligands normally induced by TCR signaling in untransformed T cells. Until recently, their molecular mechanisms were unclear. Recently, high-dimensional studies have transformed our understanding of their cellular and genetic characteristics. Somatic mutations in the TCR signaling pathway drive lymphomagenesis by disrupting autoinhibitory domains, increasing affinity to ligands, and/or inducing TCR-independent signaling. Collectively, most of these mutations augment signaling pathways downstream of the TCR. Emerging data suggest that these mutations not only drive proliferation but also determine lymphoma immunophenotypes. For example, RHOA mutations are sufficient to induce disease-relevant CD4+ T follicular helper cell phenotypes. In this review, we describe how mutations in the TCR signaling pathway elucidate lymphoma pathophysiology but also provide insights into broader T cell biology.
Identifiants
pubmed: 37931208
pii: 266277
doi: 10.4049/jimmunol.2200682
pmc: PMC10715708
mid: NIHMS1908071
doi:
Substances chimiques
Receptors, Antigen, T-Cell
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1450-1458Subventions
Organisme : NCI NIH HHS
ID : R01 CA260064
Pays : United States
Informations de copyright
Copyright © 2023 by The American Association of Immunologists, Inc.
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