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- Title
Evolution and modulation of antigen-specific T cell responses in melanoma patients.
- Authors
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
- Abstract
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. Previous studies have characterized the diversity and dynamics of the T cell receptor (TCR) repertoire in patients with solid cancer. Here, by analyzing TCR repertoire data from multiple datasets, the authors report that melanoma-associated antigen-specific TCRs can be used to separate metastatic melanoma patients from healthy controls and to follow anti-tumor responses in patients treated with immunotherapy.
- Subjects
REGULATORY T cells; T cell receptors; T cells; MELANOMA; FATIGUE (Physiology); CANCER patients
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-33720-z