| Autor: |
Masson, Adèle de, Darbord, Delphine, Dobos, Gabor, Boisson, Marie, Roelens, Marie, Ram-Wolff, Caroline, Cassius, Charles, Le Buanec, Hélène, de la Grange, Pierre, Jouenne, Fanélie, Louveau, Baptiste, Sadoux, Aurélie, Bouaziz, Jean-David, Marie-Cardine, Anne, Bagot, Martine, Moins-Teisserenc, Hélène, Mourah, Samia, Battistella, Maxime |
| Zdroj: |
Blood; 20210101, Issue: Preprints |
| Abstrakt: |
Cutaneous T-celllymphomas (CTCL) are rare malignanciesinvolvingprimarily the skin. Responses to treatment are usually short-lived in advanced CTCL. The determinants of long-term CTCL control are unclear. Mogamulizumab, an anti-human CCR4 antibodythatacts by antibody-dependentcellcytotoxicityagainst CCR4+ CTCL tumorcells and peripheral memory blood regulatory T cells, has been associatedwith long-lasting remissions and immune adverse events. Here, wereported skin rashes in 32% of 44 CTCL patients treatedwithmogamulizumab, associatedwithsignificantlyhigheroverallsurvival (hazard ratio, 0.16 (0.04-0.73, p=0.01)). Rash occurred in Sézary patients and wasassociatedwith longer time to progression. These rashes werecharacterized by a CD163+ granulomatous and/or CD8+ lichenoid skin infiltrate. High-throughputsequencinganalysis of TCRβ genes in skin, and blood flow cytometry, confirmed the depletion of CTCL tumorcells, and the recruitment of new reactive T-cell clones in skin at the time of skin rash. CXCL9 and CXCL11, two macrophage-derivedchemokinesthatrecruit CXCR3+ T-cells to skin, wereoverexpressed in skin rashes. A higherfrequency of TIGIT+ and PD1+ exhaustedreactive blood T-cellwasobserved at baseline in patients with rash, and thisfrequencydecreaseduponmogamulizumabtreatment. These data are consistent withmogamulizumab-induced long-term immune CTCL control by activation of the macrophagic and T-cellresponses in patients with rash. |
| Databáze: |
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