Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation

Jani Huuhtanen*, Shady Adnan-Awad, Jason Theodoropoulos, Sofia Forstén, Rebecca Warfvinge, Olli Dufva, Jonas Bouhlal, Parashar Dhapola, Hanna Duàn, Essi Laajala, Tiina Kasanen, Jay Klievink, Mette Ilander, Taina Jaatinen, Ulla Olsson-Strömberg, Henrik Hjorth-Hansen, Andreas Burchert, Göran Karlsson, Anna Kreutzman, Harri LähdesmäkiSatu Mustjoki*

*Tämän työn vastaava kirjoittaja

Tutkimustuotos: LehtiartikkeliArticleScientificvertaisarvioitu

1 Sitaatiot (Scopus)
13 Lataukset (Pure)

Abstrakti

Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML (n = 13, N = 25), other cancers (n = 28), and healthy (n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56dim cluster with high expression of GZMA/B, PRF1, CCL3/4, and IFNG, with interactions with leukemic cells via inhibitory LGALS9–TIM3 and PVR–TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8 + TEMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.

AlkuperäiskieliEnglanti
Sivut109–125
JulkaisuLeukemia
Vuosikerta38
Varhainen verkossa julkaisun päivämäärä2023
DOI - pysyväislinkit
TilaJulkaistu - 2024
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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