Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
Cancer Immunol Immunother. 2019 Aug;68(8):1331-1340. doi: 10.1007/s00262-019-02370-4. Epub 2019 Jul 18.
Expression of inhibitors of apoptosis protein (IAP) family members is associated with poor prognosis in cancer patients. Immunity to ML-IAP (livin) and survivin has been well studied in patients with a variety of tumors. XIAP, the most potent inhibitor of apoptosis, is widely expressed in melanoma. To better define its potential role as an immunogenic target, cellular and humoral responses to XIAP were investigated in patients with advanced melanoma. An overlapping peptide library covering the full length of the XIAP protein was used to screen T cell responses of peripheral blood mononuclear cells (PBMC) from stage-IV melanoma patients treated with or without anti-CTLA4 (ipilimumab). The screen identified an array of peptides that predominantly induced CD4 T cell responses. XIAP epitope-specific CD4 T cells revealed proliferative responses to melanoma cells that express XIAP. Humoral responses to XIAP were also explored. Cellular and humoral responses to XIAP were associated with beneficial clinical outcomes after ipilimumab-based treatment, supporting XIAP as a potential therapeutic target.
凋亡抑制蛋白（IAP）家族成员的表达与癌症患者的预后不良有关。针对 ML-IAP（livin）和 survivin 的免疫反应已在多种肿瘤患者中得到了充分研究。XIAP 是凋亡的最有效抑制剂，在黑色素瘤中广泛表达。为了更好地确定其作为免疫原性靶标的潜在作用，研究了晚期黑色素瘤患者对 XIAP 的细胞和体液反应。使用覆盖 XIAP 全长的重叠肽文库筛选接受或未接受抗 CTLA4（ipilimumab）治疗的 IV 期黑色素瘤患者外周血单核细胞（PBMC）中的 T 细胞反应。该筛选确定了一组主要诱导 CD4 T 细胞反应的肽。XIAP 表位特异性 CD4 T 细胞对表达 XIAP 的黑色素瘤细胞显示出增殖反应。还探讨了针对 XIAP 的体液反应。基于 ipilimumab 的治疗后，针对 XIAP 的细胞和体液反应与有益的临床结果相关，支持 XIAP 作为潜在的治疗靶标。
