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Suma, Sakurako; Suehara, Yasuhito; Fujisawa, Manabu; Abe, Yoshiaki; Hattori, Keiichiro; Makishima, Kenichi; Sakamoto, Tatsuhiro; Sawa, Aya; Bando, Hiroko; Kaji, Daisuke; Sugio, Takeshi; Kato, Koji; Akashi, Koichi; Matsue, Kosei; Carreras, Joaquim; Nakamura, Naoya; Suzuki, Ayako; Suzuki, Yutaka; Ito, Ken; Shiiba, Hiroyuki; Chiba, Shigeru; Sakata-Yanagimoto, Mamiko
Leukemia, 02/2024, Volume: 38, Issue: 2Journal Article
T follicular helper (T ) cell lymphomas (TFHLs) are characterized by T -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 T 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 T -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.
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