{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:16:55Z","timestamp":1792603015890,"version":"4.5.0"},"reference-count":79,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"76","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,10,28]]},"abstract":"<jats:p>\n            Some hematological malignancies such as multiple myeloma are inherently resistant to immune-mediated antitumor responses, the cause of which remains unknown. Allogeneic bone marrow transplantation (alloBMT) is the only curative immunotherapy for hematological malignancies due to profound graft-versus-tumor (GVT) effects, but relapse remains the major cause of death. We developed murine models of alloBMT where the hematological malignancy is either sensitive [acute myeloid leukemia (AML)] or resistant (myeloma) to GVT effects. We found that CD8\n            <jats:sup>+<\/jats:sup>\n            T cell exhaustion in bone marrow was primarily alloantigen-driven, with expression of inhibitory ligands present on myeloma but not AML. Because of this tumor-independent exhaustion signature, immune checkpoint inhibition (ICI) in myeloma exacerbated graft-versus-host disease (GVHD) without promoting GVT effects. Administration of post-transplant cyclophosphamide (PT-Cy) depleted donor T cells with an exhausted phenotype and spared T cells displaying a stem-like memory phenotype with chromatin accessibility present in cytokine signaling genes, including the interleukin-18 (IL-18) receptor. Whereas ICI with anti\u2013PD-1 or anti\u2013TIM-3 remained ineffective after PT-Cy, administration of a decoy-resistant IL-18 (DR-18) strongly enhanced GVT effects in both myeloma and leukemia models, without exacerbation of GVHD. We thus defined mechanisms of resistance to T cell\u2013mediated antitumor effects after alloBMT and described an immunotherapy approach targeting stem-like memory T cells to enhance antitumor immunity.\n          <\/jats:p>","DOI":"10.1126\/sciimmunol.abo3420","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T17:58:23Z","timestamp":1665770303000},"source":"Crossref","is-referenced-by-count":35,"title":["Depletion of exhausted alloreactive T cells enables targeting of stem-like memory T cells to generate tumor-specific immunity"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1314-9264","authenticated-orcid":true,"given":"Simone A.","family":"Minnie","sequence":"first","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7021-0431","authenticated-orcid":true,"given":"Olivia G.","family":"Waltner","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen S.","family":"Ensbey","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole S.","family":"Nemychenkov","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine R.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti S.","family":"Bhise","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel R. 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Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1318-2902","authenticated-orcid":true,"given":"Danniel","family":"Zamora","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Washington, Seattle, WA 98109, USA."},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-7360","authenticated-orcid":true,"given":"Albert","family":"Yeh","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA."},{"name":"Department of Medicine, University of Washington, Seattle, WA 98109, 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