Casati Chiara, Dalerba Piero, Rivoltini Licia, Gallino Gianfrancesco, Deho Paola, Rini Francesca, Belli Filiberto, Mezzanzanica Delia, Costa Aurora, Andreola Salvatore, Leo Ermanno, Parmiani Giorgio, Castelli Chiara
Unit of Immunotherapy of Human Tumors, Department of Pathology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via G. Venezian 1, 20133 Milan, Italy.
Cancer Res. 2003 Aug 1;63(15):4507-15.
The identification of tumor-associated antigens expressed by colorectal carcinoma remains one of the major goals for designing novel immunological treatments for this tumor. By using a reverse-immunology approach, we show here that the inhibitor of apoptosis protein, survivin, is immunogenic in colorectal cancer patients. In particular, we found that survivin elicited CD8(+) T cell-mediated responses in peripheral blood or in tumor-associated lymphocytes from patients at different disease stage. Colorectal carcinoma cells were recognized by survivin-specific T lymphocytes, and the survivin-specific, class-I HLA-restricted T lymphocytes were fully activated and released interleukin-2 in response to HLA/survivin-peptide complexes expressed by tumor cells. In addition to CD8-mediated responses, survivin specifically stimulated CD4+ T-cell reactivity in peripheral blood lymphocytes from the same patients, thus suggesting that a complete activation of the immune system may occur in response to this antiapoptotic protein. These findings indicate that survivin could be considered a valuable tumor-associated antigen for immune-based clinical approaches in colorectal cancer.
鉴定结直肠癌表达的肿瘤相关抗原仍然是设计针对该肿瘤的新型免疫治疗方法的主要目标之一。通过采用反向免疫学方法，我们在此表明凋亡抑制蛋白survivin在结直肠癌患者中具有免疫原性。具体而言，我们发现survivin在不同疾病阶段患者的外周血或肿瘤相关淋巴细胞中引发了CD8(+) T细胞介导的反应。结直肠癌细胞被survivin特异性T淋巴细胞识别，并且survivin特异性的、I类HLA限制性T淋巴细胞被完全激活，并响应肿瘤细胞表达的HLA/survivin肽复合物释放白细胞介素-2。除了CD8介导的反应外，survivin还特异性刺激了同一患者外周血淋巴细胞中的CD4+ T细胞反应性，因此表明针对这种抗凋亡蛋白可能会发生免疫系统的完全激活。这些发现表明，survivin可被视为结直肠癌基于免疫的临床方法中有价值的肿瘤相关抗原。
