Browsing by Author "Kasanen, Henna"

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Evolution and modulation of antigen-specific T cell responses in melanoma patients
(2022-10-11) Huuhtanen, Jani; Chen, Liang; Jokinen, Emmi; Kasanen, Henna; Lönnberg, Tapio; Kreutzman, Anna; Peltola, Katriina; Hernberg, Micaela; Wang, Chunlin; Yee, Cassian; Lähdesmäki, Harri; Davis, Mark M.; Mustjoki, Satu
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Analyzing antigen-specific T cell responses at scale has been challenging. Here, we analyze three types of T cell receptor (TCR) repertoire data (antigen-specific TCRs, TCR-repertoire, and single-cell RNA + TCRαβ-sequencing data) from 515 patients with primary or metastatic melanoma and compare it to 783 healthy controls. Although melanoma-associated antigen (MAA) -specific TCRs are restricted to individuals, they share sequence similarities that allow us to build classifiers for predicting anti-MAA T cells. The frequency of anti-MAA T cells distinguishes melanoma patients from healthy and predicts metastatic recurrence from primary melanoma. Anti-MAA T cells have stem-like properties and frequent interactions with regulatory T cells and tumor cells via Galectin9-TIM3 and PVR-TIGIT -axes, respectively. In the responding patients, the number of expanded anti-MAA clones are higher after the anti-PD1(+anti-CTLA4) therapy and the exhaustion phenotype is rescued. Our systems immunology approach paves the way for understanding antigen-specific responses in human disorders.
Single-cell characterization of anti-LAG-3 and anti-PD-1 combination treatment in patients with melanoma
(2023-03-15) Huuhtanen, Jani; Kasanen, Henna; Peltola, Katriina; Lönnberg, Tapio; Glumoff, Virpi; Brück, Oscar; Dufva, Olli; Peltonen, Karita; Vikkula, Johanna; Jokinen, Emmi; Ilander, Mette; Lee, Moon Hee; Mäkelä, Siru; Nyakas, Marta; Li, Bin; Hernberg, Micaela; Bono, Petri; Lähdesmäki, Harri; Kreutzman, Anna; Mustjoki, Satu
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
BACKGROUND. Relatlimab plus nivolumab (anti-lymphocyte-activation gene 3 plus anti-programmed death 1 [anti-LAG-3+anti-PD-1]) has been approved by the FDA as a first-line therapy for stage III/IV melanoma, but its detailed effect on the immune system is unknown. METHODS. We evaluated blood samples from 40 immunotherapy-naive or prior immunotherapy-refractory patients with metastatic melanoma treated with anti-LAG-3+anti-PD-1 in a phase I trial using single-cell RNA and T cell receptor sequencing (scRNA+TCRαβ-Seq) combined with other multiomics profiling. RESULTS. The highest LAG3 expression was noted in NK cells, Tregs, and CD8+ T cells, and these cell populations underwent the most significant changes during the treatment. Adaptive NK cells were enriched in responders and underwent profound transcriptomic changes during the therapy, resulting in an active phenotype. LAG3+ Tregs expanded, but based on the transcriptome profile, became metabolically silent during the treatment. Last, higher baseline TCR clonality was observed in responding patients, and their expanding CD8+ T cell clones gained a more cytotoxic and NK-like phenotype. CONCLUSION. Anti-LAG-3+anti-PD-1 therapy has profound effects on NK cells and Tregs in addition to CD8+ T cells. TRIAL REGISTRATION. ClinicalTrials.gov (NCT01968109) FUNDING. Cancer Foundation Finland, Sigrid Juselius Foundation, Signe and Ane Gyllenberg Foundation, Relander Foundation, State funding for university-level health research in Finland, a Helsinki Institute of Life Sciences Fellow grant, Academy of Finland (grant numbers 314442, 311081, 335432, and 335436), and an investigator-initiated research grant from BMS.