Evolution and modulation of antigen-specific T cell responses in melanoma patients

Jani Huuhtanen, Liang Chen, Emmi Jokinen, Henna Kasanen, Tapio Lönnberg, Anna Kreutzman, Katriina Peltola, Micaela Hernberg, Chunlin Wang, Cassian Yee, Harri Lähdesmäki, Mark M. Davis, Satu Mustjoki*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

3 Citations (Scopus)
27 Downloads (Pure)


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.

Original languageEnglish
Article number5988
Pages (from-to)1-14
Number of pages14
JournalNature Communications
Issue number1
Publication statusPublished - 11 Oct 2022
MoE publication typeA1 Journal article-refereed


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