Tumor heterogeneity and immune-evasive T follicular cell lymphoma phenotypes at single-cell resolution.
Leukemia
; 38(2): 340-350, 2024 02.
Article
in En
| MEDLINE
| ID: mdl-38012392
ABSTRACT
T follicular helper (TFH) cell lymphomas (TFHLs) are characterized by TFH-like properties and accompanied by substantial immune-cell infiltration into tumor tissues. Nevertheless, the comprehensive understanding of tumor-cell heterogeneity and immune profiles of TFHL remains elusive. To address this, we conducted single-cell transcriptomic analysis on 9 lymph node (LN) and 16 peripheral blood (PB) samples from TFHL patients. Tumor cells were divided into 5 distinct subclusters, with significant heterogeneity observed in the expression levels of TFH markers. Copy number variation (CNV) and trajectory analyses indicated that the accumulation of CNVs, together with gene mutations, may drive the clonal evolution of tumor cells towards TFH-like and cell proliferation phenotypes. Additionally, we identified a novel tumor-cell-specific marker, PLS3. Notably, we found a significant increase in exhausted CD8+ T cells with oligoclonal expansion in TFHL LNs and PB, along with distinctive immune evasion characteristics exhibited by infiltrating regulatory T, myeloid, B, and natural killer cells. Finally, in-silico and spatial cell-cell interaction analyses revealed complex networking between tumor and immune cells, driving the formation of an immunosuppressive microenvironment. These findings highlight the remarkable tumor-cell heterogeneity and immunoevasion in TFHL beyond previous expectations, suggesting potential roles in treatment resistance.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphoma, Follicular
/
T-Lymphocytes, Helper-Inducer
Limits:
Humans
Language:
En
Journal:
Leukemia
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
Japan