Effector CD4 and CD8 T cells and their role in the tumor microenvironment.
Effector CD4 and CD8 T cells and their role in the tumor microenvironment.
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DOI：
10.1007/s12307-012-0127-6
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发表时间：
2013-08
影响因子：
--
通讯作者：
Thor Straten, Per
中科院分区：
文献类型：
--
作者：
Hadrup, Sine;Donia, Marco;Thor Straten, Per
肿瘤中的T细胞--肿瘤浸润淋巴细胞（tumor infiltrating lymphocytes，TIL）近年来受到广泛的研究。令人信服的证据表明，肿瘤部位大量T细胞与CD 8记忆T细胞的临床相关性是结肠直肠癌（CRC）患者以及其他实体癌患者总生存期（OS）的关键分母。这些数据与TIL的克隆性研究密切相关，显示TIL中的T细胞克隆性扩增，并且CD 4和CD 8型的肿瘤特异性T细胞在肿瘤部位富集。肿瘤微环境不利于T细胞功能，例如，这是由于表达了耗尽氨基酸色氨酸和精氨酸的酶、高浓度的肿瘤分泌的乳酸盐以及存在具有抑制活性的先天性细胞或调节性T细胞。对黑素瘤中TIL的特异性的分析表明，事实上很少有已知抗原被这些培养物识别，这强调了患者独特和/或突变的抗原可能代表识别的重要靶标。
T cells in tumors—the so-called tumor infiltrating lymphocytes (TIL) have been studied intensively over the past years. Compelling evidence point to a clinical relevance for high numbers of T cells at the tumor site with CD8 memory T cells as a key denominator for overall survival (OS) in patients with colo-rectal cancer (CRC), and also for others solid cancers. These data goes hand in hand with studies of clonality of TIL showing the T cells among TIL are expanded clonally, and also that tumor specific T cells of CD4 as well as CD8 type are enriched at the tumor site. The tumor microenvironment is hostile to T cell function e.g., due to expression of enzymes that depletes the amino acids tryptophan and arginine, high concentration of tumor secreted lactate, and presence innate cells or regulatory T cells both with suppressive activity. Analyses of the specificity of TILs in melanoma demonstrate that quite few known antigens are in fact recognized by these cultures underscoring patient unique and/or mutated antigens may represent important target for recognition.