Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration.
Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration.
复制标题
给予泊马度胺后患有卡波西肉瘤的参与者的免疫表型分析。
DOI：
10.1097/qad.0000000000003627
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Sereti,Irini
中科院分区：
文献类型：
--
作者：
Lurain,Kathryn;Polizzotto,MarkN;Krug,LaurieT;Shoemaker,Griffin;Singh,Amrit;Jensen,StigMR;Wyvill,KathleenM;Ramaswami,Ramya;Uldrick,ThomasS;Yarchoan,Robert;Sereti,Irini
Objective:The aim of this study was to evaluate baseline differences by HIV status and the impact of pomalidomide on lymphocyte counts and T-cell subsets in patients with Kaposi sarcoma.Design:We prospectively evaluated CD4+ and CD8+ T-cell phenotypes in 19 participants with Kaposi sarcoma enrolled on a phase 1/2 study of pomalidomide (NCT01495598), seven without HIV and 12 with HIV on antiretroviral therapy.Methods:Trial participants received pomalidomide 5 mg orally for 21 days of 28-day cycles for up to 1 year. Flow cytometry was performed on peripheral blood mononuclear cells at baseline, after three cycles, and at end-of-treatment. Lymphocyte count and T-cell subset comparisons were evaluated by Wilcoxon signed-rank and Mann--Whitney tests.Results:At baseline, HIV+ participants had lower CD4+ cell counts (median 416 vs. 742 CD4+ T cells/μl, P= 0.006), and a decreased proportion of CD57+(senescent) CD8+ T cells (P= 0.007) compared with HIV-participants. After three cycles, pomalidomide led to an increased proportion of CD45RO+ CD27+(central memory) CD4+(P= 0.002) and CD8+(P= 0.002) T cells, a decrease in CD45RO-CD27-(effector) CD4+ cells (P= 0.0002), and expansion of CD38+/HLADR+(activated) CD4+(P= 0.002) and CD8+(P≤ 0.0001) T cells. Increased numbers of activated CD8+ T cells persisted at end-of-treatment (P= 0.002). After three cycles and at end-of-treatment, there was reduction in the proportion of CD57+(senescent) CD4+(P= 0.001, 0.0006), and CD8+(P=< 0.0001, 0.0004) T cells.Conclusion:Administration of pomalidomide decreased T-cell senescence and increased T-cell activation in patients with Kaposi sarcoma, suggesting pomalidomide activity in Kaposi sarcoma stems in part from its immunomodulatory effects.
