Cytotoxic T Lymphocytes Efficiently Recognize Human Colon Cancer Stem-Like Cells
Cytotoxic T Lymphocytes Efficiently Recognize Human Colon Cancer Stem-Like Cells
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DOI：
10.1016/j.ajpath.2011.01.004
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发表时间：
2011-04-01
影响因子：
6
通讯作者：
Sato, Noriyuki
中科院分区：
文献类型：
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作者：
Inoda, Satoko;Hirohashi, Yoshihiko;Sato, Noriyuki
癌症干细胞样细胞（CSC）和肿瘤起始细胞（TIC）是一小群癌细胞，具有三种特性：肿瘤起始能力，自我更新和分化。这些特性表明CSC/TIC对于肿瘤维持、复发和远处转移是必不可少的。在这里，我们表明，细胞毒性T淋巴细胞（CTL）的肿瘤相关抗原CEP 55特异性可以有效地识别结肠CSC/TIC在体外和体内。使用Hoechst 33342染料染色，我们从结肠癌细胞系SW 480、HT 29和HCT 15中分离CSC/TIC作为侧群（SP）细胞。SP细胞表达高水平的干细胞标志物SOX 2、POU 5 F1、LGR 5和ALDH 1A 1，并显示出对化疗药物如伊立替康或依托泊苷的抗性。为了评估SP细胞对CTI的敏感性，我们使用CTL克隆41，其对CEP 55衍生的抗原肽Cep 55/c10orf3_193（10）（VYVKGLLAKI）具有特异性。SP细胞以与主要群体细胞相同的水平表达HLA I类和CEP 55。SP细胞对CTL克隆41的敏感性与主群细胞相同。此外，过继转移CTL克隆41抑制SW 480 SP细胞的体内肿瘤生长。这些观察结果表明，基于Cep 55/c10orf3_193（10）肽的癌症疫苗疗法或CTL克隆的过继细胞转移是靶向化疗抗性结肠CSC/TIC的可能方法。(Am J Pathol 2011，178：1805-1813; DOI：10.1016/j.ajpath.2011.01.004）
Cancer stem-like cells (CSCs) and tumor-initiating cells (TICs) are a small population of cancer cells that share three properties: tumor initiating ability, self-renewal, and differentiation. These properties suggest that CSCs/TICs are essential for tumor maintenance, recurrence, and distant metastasis. Here, we show that cytotoxic T lymphocytes (CTLs) specific for the tumor-associated antigen CEP55 can efficiently recognize colon CSCs/TICs both in vitro and in vivo. Using Hoechst 33342 dye staining, we isolated CSCs/TICs as side population (SP) cells from colon cancer cell lines SW480, HT29, and HCT15. The SP cells expressed high levels of the stem cell markers SOX2, POU5F1, LGR5, and ALDH1A1 and showed resistance to chemotherapeutic agents such as irinotecan or etoposide. To evaluate the susceptibility of SP cells to CTIs, we used CTL clone 41, which is specific for the CEP55-derived antigenic peptide Cep55/c10orf3_193 (10) (VYVKGLLAKI). The SP cells expressed HLA class I and CEP55 at the same level as the main population cells. The SP cells were susceptible to CTL clone 41 at the same level as main population cells. Furthermore, adoptive transfer of CTL clone 41 inhibited tumor growth of SW480 SP cells in vivo. These observations suggest that Cep55/c10orf3_193(10) peptide-based cancer vaccine therapy or adoptive cell transfer of the CTL clone is a possible approach for targeting chemotherapy-resistant colon CSCs/TICs. (Am J Pathol 2011, 178:1805-1813; DOI: 10.1016/j.ajpath.2011.01.004)