Discrete genetic subtypes and tumor microenvironment signatures correlate with peripheral T-cell lymphoma outcomes
Peripheral T-cell lymphoma (PTCL) exhibits a diverse clinical spectrum, necessitating methods to categorize patients based on genomic abnormalities or tumor microenvironment (TME) profiles. We conducted an integrative multiomics study in 129 PTCL patients, performing whole-exome sequencing and identifying three genetic subtypes: C1, C2, and C3. C2 was characterized by loss of tumor suppressor genes and chromosomal instability, while C1 and C3 shared T follicular helper (TFH)-related genomic alterations, with C3 also showing a high incidence of IDH2 mutations and chromosome 5 gain. Compared to C1, survival was significantly worse in C2 (HR 2.52; 95% CI, 1.37-4.63) and C3 (HR 2.14; 95% CI, 1.17-3.89). We also estimated the proportions of immune cell fractions from the bulk RNA sequencing data using CIBERSORTx and classified TME signatures into the following hierarchical clusters: TME1 (characterized by increased B and TFH cells), TME2 (macrophages), and TME3 (activated mast cells). TME2 was associated with shorter survival (HR 3.4; 95% CI, 1.6-7.5) and was more frequent in C2 (64.3%) than in C1 (7.7%), whereas C1 had more TME3 signatures (80.8% vs. 28.6%). These findings highlight a significant relationship between genetic subtypes and TME signatures in PTCL, with important implications for clinical prognosis.
Authors
- Kohshi Hattori (ORCID: https://orcid.org/0000-0001-6415-4082)
- Takeshi Sugio (ORCID: https://orcid.org/0000-0002-4270-1943)
- Kenichi Makishima (ORCID: https://orcid.org/0000-0002-5808-816X)
- Mamiko Sakata‐Yanagimoto (ORCID: https://orcid.org/0000-0001-7310-8045)
- Kentaro Narita (ORCID: https://orcid.org/0000-0002-6504-9046)
- Shigeru Chiba (ORCID: https://orcid.org/0000-0001-9458-5713)
- Yuichi Shiraishi (ORCID: https://orcid.org/0000-0001-6144-5845)
- Naoya Nakamura
- Yoshiaki Abe (ORCID: https://orcid.org/0000-0002-1021-7911)
- Kengo Takeuchi (ORCID: https://orcid.org/0000-0002-1599-5800)
- Sakurako Suma (ORCID: https://orcid.org/0000-0003-2491-3798)
- Tatsuhiro Sakamoto (ORCID: https://orcid.org/0000-0001-6852-0721)
- Seishi Ogawa (ORCID: https://orcid.org/0000-0002-7778-5374)
- Kenichi Chiba
- Yasuhito Suehara (ORCID: https://orcid.org/0000-0001-7046-2196)
- Kosei Matsue
- Kana Sakamoto (ORCID: https://orcid.org/0000-0003-0815-3741)
- Joaquim Carreras (ORCID: https://orcid.org/0000-0002-6129-8299)
- Satoru Miyano (ORCID: https://orcid.org/0000-0002-1753-6616)
- Kota Fukumoto (ORCID: https://orcid.org/0000-0002-2729-5780)
- Koji Kato
- Koichi Akashi (ORCID: https://orcid.org/0000-0001-7763-5723)
- Manabu Fujisawa (ORCID: https://orcid.org/0009-0007-1122-6549)
Institutions
- Tokyo Medical and Dental University (JP)
- Tokai University (JP)
- Kyushu University (JP)
- University of Tsukuba (JP)
- Kyoto University (JP)
- Spinal Cord Injury BC (CA)
- Kameda Medical Center (JP)
- University of Tsukuba Hospital (JP)
- Tsukuba Medical Center Hospital (JP)
- Japanese Foundation For Cancer Research (JP)
- Stanford University (US)
Publication Details
- Journal
- Leukemia
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1038/s41375-025-02563-0
- Citations
- 6
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 8.83
Funders
- Leukemia and Lymphoma Society
- Gilead Sciences
- Japan Agency for Medical Research and Development
- Kobayashi Foundation for Cancer Research
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Moonshot Research and Development Program