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Cited by 105Cutaneous lymphoproliferative disorders researchLymphoma Diagnosis and TreatmentCancer and Skin Lesions

Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas

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Daniels, Jay, Doukas, Peter G., Escala, Maria E. Martinez, Ringbloom, Kimberly G., Shih, David J. H., Yang, Jingyi, Tegtmeyer, Kyle, Park, Joonhee +16 more·2020·Nature Communications
DOI 10.1038/s41467-020-15572-7PMC PMC7156460
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Abstract

Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.

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  • IL-17 release by DETCs can promote DNA repair following exposure to UV radiation and protect the skin against potential opportunistic infections by releasing keratinocyte-derived antimicrobial peptides.

    “IL-17 release by DETCs can promote DNA repair following exposure to UV radiation and protect the skin against potential opportunistic infections by releasing keratinocyte-derived antimicrobial peptides (37, 38).”

    From Comparing Mouse and Human Tissue-Resident γδ T Cells (2022) · cites this paper as [38]

    The Discussion (page not provided) says that, in mouse models, γδ T cells protect against microbes and contribute to epidermal homeostasis. It does not say that DETC-derived IL-17 promotes DNA repair after UV exposure or that keratinocyte-derived antimicrobial peptides provide the claimed protection. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Daniels, J., Doukas, P. G., Escala, M. E. M., Ringbloom, K. G., Shih, D. J. H., Yang, J., Tegtmeyer, K., Park, J., Thomas, J. J., Selli, M. E., Altunbulakli, C., Gowthaman, R., Mo, S. H., Jothishankar, B., Pease, D. R., Pro, B., Abdulla, F. R., Shea, C., Sahni, N., Gru, A. A., Pierce, B. G., Louissaint, A., Guitart, J., & Choi, J.
Affiliations
  • Northwestern University (US)
  • The University of Texas MD Anderson Cancer Center (US)
  • Institute for Bioscience and Biotechnology Research (US)
  • University of Illinois Chicago (US)
  • University of Chicago (US)
  • City Of Hope National Medical Center (US)
  • University of Virginia Health System (US)
  • Massachusetts General Hospital (US)
Corresponding author
  • Louissaint, Abner
  • Guitart, Joan
  • Choi, Jaehyuk
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-04-14
Volume
11
Issue
1
Pages
1806-1806
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-15572-7
PMC
PMC7156460
OpenAlex
W3016153237
Cited by
105
References
4
Citations by year
2026: 7 · 2025: 14 · 2024: 19 · 2023: 22 · 2022: 18 · 2021: 20 · 2020: 4
FWCI
11.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (T32 CA009560, K08-CA191019-01A1)
  • U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (T35DK062719-29)
  • Cancer Prevention and Research Institute of Texas (RR160021)
  • Alfred P. Sloan Foundation (FG-2018-10723)
  • U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R01 GM126299)
  • U.S. Department of Health & Human Services | National Institutes of Health (1DP2AI136599-01)
  • American Cancer Society (ACS-IRG-15-173-21)
  • Leukemia Research Foundation (n/a)
  • Damon Runyon Cancer Research Foundation (DRCRF# CI-84-16)
  • Doris Duke Charitable Foundation (DDCF# 2016095)
  • Skin Cancer Foundation (n/a)
Topics
  • Health Sciences › Medicine › Dermatology › Cutaneous lymphoproliferative disorders research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Dermatology › Cancer and Skin Lesions
Keywords
primary cutaneous gamma-delta T-cell lymphoma, Vδ1 T cells, Vδ2 T cells, cell of origin, T cell receptor repertoire, genomic landscape, JAK/STAT signaling, MAPK signaling, c-Myc, chromatin modification, epidermis, dermis, skin fat
MeSH terms
Amino Acid Sequence, Epitopes, Humans, Lymph Nodes, Models, Biological, Mutation, Phenotype, Skin, Skin Neoplasms, Transcription, Genetic, Signal Transduction, Genome, Human, Lymphoma, T-Cell, Cutaneous, Receptors, Antigen, T-Cell, gamma-delta, Principal Component Analysis, Chromatin Assembly and Disassembly, Antigens, CD1d, HEK293 Cells, Transcriptome

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