{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:33:00Z","timestamp":1772717580533,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-2 is critical for peripheral tolerance mediated by regulatory T (Treg) cells, which represent an obstacle for effective cancer immunotherapy. Although IL-2 is important for effector (E) T cell function, it has been hypothesized that therapies blocking IL-2 signals weaken Treg cell activity, promoting immune responses. This hypothesis has been partially tested using anti\u2013IL-2 or anti\u2013IL-2R Abs with antitumor effects that cannot be exclusively attributed to lack of IL-2 signaling in vivo. In this work, we pursued an alternative strategy to block IL-2 signaling in vivo, taking advantage of the trimeric structure of the IL-2R. We designed an IL-2 mutant that conserves the capacity to bind to the \u03b1\u03b2-chains of the IL-2R but not to the \u03b3c-chain, thus having a reduced signaling capacity. We show our IL-2 mutein inhibits IL-2 Treg cell\u2013dependent differentiation and expansion. Moreover, treatment with IL-2 mutein reduces Treg cell numbers and impairs tumor growth in mice. A mathematical model was used to better understand the effect of the mutein on Treg and E T cells, suggesting suitable strategies to improve its design. Our results show that it is enough to transiently inhibit IL-2 signaling to bias E and Treg cell balance in vivo toward immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1700433","type":"journal-article","created":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T15:40:26Z","timestamp":1522856426000},"page":"3475-3484","source":"Crossref","is-referenced-by-count":53,"title":["Blocking IL-2 Signal In Vivo with an IL-2 Antagonist Reduces Tumor Growth through the Control of Regulatory T Cells"],"prefix":"10.1093","volume":"200","author":[{"given":"Tania","family":"Carmenate","sequence":"first","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"given":"Yaquel\u00edn","family":"Ort\u00edz","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7748-454X","authenticated-orcid":false,"given":"Michel","family":"Enamorado","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"given":"Karina","family":"Garc\u00eda-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"given":"Janet","family":"Avellanet","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2309-4826","authenticated-orcid":false,"given":"Ernesto","family":"Moreno","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]},{"given":"Luis","family":"Gra\u00e7a","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa , 1649-028 Lisbon,","place":["Portugal"]}]},{"given":"Kalet","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Centro de Inmunolog\u00eda Molecular , 16040 Havana,","place":["Cuba"]}]}],"member":"286","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"2025030610150417800_r1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1359-6101(97)00021-X","article-title":"Signaling from the IL-2 receptor to the nucleus","volume":"8","author":"Lin","year":"1997","journal-title":"Cytokine Growth Factor Rev."},{"key":"2025030610150417800_r2","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.181845","article-title":"Selective in vitro growth of T lymphocytes from normal human bone marrows","volume":"193","author":"Morgan","year":"1976","journal-title":"Science"},{"key":"2025030610150417800_r3","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1189\/jlb.0603272","article-title":"The main function of IL-2 is to promote the development of T regulatory cells","volume":"74","author":"Malek","year":"2003","journal-title":"J. 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