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T-cell immunotherapies targeting WT1 are currently under development. To analyze endogenous T-cell responses against WT1, we trained computational models capable of detecting WT1-specific T-cell responses from T-cell receptor (TCR) sequencing data. We peptide-pulsed healthy donor and acute myeloid leukemia (AML) patient samples with VLDFAPPGA (VLD, WT1\n                    <jats:sub>37-45<\/jats:sub>\n                    ) and RMFPNAPYL (RMF, WT1\n                    <jats:sub>126-134<\/jats:sub>\n                    ) peptides, then sequenced the WT1 dextramer-positive CD8\u2009+\u2009T-cells with single-cell RNA\u2009+\u2009TCR\u03b1\u03b2 sequencing. The TCRGP machine-learning TCR-classification method was trained with epitope-specific and control TCR repertoires, and we obtained AUROC values of 0.74 (VLD) and 0.75 (RMF), allowing reliable identification of WT1-specific T-cells. In bulk TCR\u03b2 sequenced patient samples (AML n\u2009=\u200921, chronic myeloid leukemia (CML) n\u2009=\u200926, and myelodysplastic syndrome n\u2009=\u200925), the median WT1-specific T-cell abundance was similar to healthy controls, but their VLD and RMF-specific TCR repertoires exhibited higher clonality with two patients presenting up to 13% of WT1-specific T-cells. ScRNA+TCR\u03b1\u03b2 sequencing of AML bone marrow T-cells revealed that WT1-specific T-cells predominantly exhibit an effector or terminal effector memory phenotype. In conclusion, our novel computational models enable large-scale WT1-specific T-cell identification from TCR sequencing datasets and leukemia-antigen-specific immune response monitoring.\n                  <\/jats:p>","DOI":"10.1038\/s41375-025-02727-y","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T18:21:22Z","timestamp":1755886882000},"page":"2767-2778","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicting antigen-specific T-cell immunity against Wilms tumor 1 in hematologic cancer"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2301-7799","authenticated-orcid":false,"given":"Brittany L.","family":"Ford","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmi","family":"Jokinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-4033","authenticated-orcid":false,"given":"Jani","family":"Huuhtanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4835-3334","authenticated-orcid":false,"given":"Sofia","family":"Forst\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay","family":"Klievink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9388-8632","authenticated-orcid":false,"given":"Gabriella","family":"Antignani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-9419","authenticated-orcid":false,"given":"Oscar","family":"Br\u00fcck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Cerullo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"iCAN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3063-451X","authenticated-orcid":false,"given":"Karita","family":"Peltonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-8241","authenticated-orcid":false,"given":"Satu","family":"Mustjoki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"2727_CR1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1006\/excr.2000.5131","volume":"264","author":"SB Lee","year":"2001","unstructured":"Lee SB, Haber DA. 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VC is a co-founder and shareholder of Valo Therapeutics LTD (unrelated). OB declares consultancy fees from Novartis, Sanofi, Roche, GSK, and Amgen; research grants from Pfizer and Gilead Sciences; stock ownership of Hematoscope Ltd (unrelated). JH declares consultancy fees from Daiichi-Sankyo (unrelated). The other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}