{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:43:48Z","timestamp":1772779428561,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T00:00:00Z","timestamp":1475107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,11]]},"abstract":"Abstract<\/jats:title>CD1d<\/jats:styled-content>\u2010restricted invariant natural killer T (iNKT<\/jats:styled-content>) cells are believed to play a key role in cancer immune surveillance, and are functionally deficient in patients with chronic myeloid leukaemia (CML<\/jats:styled-content>). Herein, we have hypothesized that this defect might originate from BCR\u2010ABL<\/jats:styled-content>\u2010dependent dysfunctions in myeloid dendritic cells (mDCs<\/jats:styled-content>). Indeed, flow cytometry and confocal microscopy revealed that cell surface expression of CD1d<\/jats:styled-content> was downregulated in CML mDCs<\/jats:styled-content>, relative to healthy donor (HD<\/jats:styled-content>) controls. The decreased cell surface display of CD1d<\/jats:styled-content> could not be ascribed to defective mDC<\/jats:styled-content> differentiation, as attested by normal expression of HLA\u2010DR<\/jats:styled-content> and the CD86<\/jats:styled-content> maturation marker. On the other hand, reduced membrane expression was not associated with decreased intracytoplasmic levels of CD1d<\/jats:styled-content> or its mRNA<\/jats:styled-content> transcripts, consistent with intracellular retention. In vitro<\/jats:italic> treatment of CML mDCs<\/jats:styled-content> with the Rho\u2010associated protein kinase (ROCK<\/jats:styled-content>) inhibitor Y\u201027632 partially restored both cell surface CD1d<\/jats:styled-content> expression and CD1d<\/jats:styled-content>\u2010mediated antigen presentation, whereas it had no effect on HD mDCs<\/jats:styled-content>. An inhibitor of BCR\u2010ABL<\/jats:styled-content> tyrosine kinase (TK<\/jats:styled-content>), imatinib mesylate (IM), had no such activity. Similar recovery of CD1d<\/jats:styled-content> expression occurred with fasudil, another ROCK<\/jats:styled-content> inhibitor that is commonly used in clinical trials. Our data support the conclusion that BCR\u2010ABL<\/jats:styled-content>\u2010dependent ROCK<\/jats:styled-content>, but not TK<\/jats:styled-content>, is involved in CD1d<\/jats:styled-content> downregulation. We propose that ROCK<\/jats:styled-content>, which is most likely activated by the DH<\/jats:styled-content>\/PH<\/jats:styled-content> domain of BCR\u2010ABL<\/jats:styled-content>, mediates iNKT<\/jats:styled-content>\u2010cell immune subversion in CML<\/jats:styled-content> patients by downregulating CD1d<\/jats:styled-content> expression on CML mDCs<\/jats:styled-content>. Our study reveals the ROCK\u2013mDC<\/jats:styled-content> axis as a new potential target to restore immune surveillance in patients with CML<\/jats:styled-content>, offering new therapeutic perspectives for CML<\/jats:styled-content> treatment. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. 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