Sokol Lena, Koelzer Viktor H, Rau Tilman T, Karamitopoulou Eva, Zlobec Inti, Lugli Alessandro
Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland.
Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland.
J Transl Med. 2015 Aug 27;13:279. doi: 10.1186/s12967-015-0647-1.
Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival.
A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging.
A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95% CI 1.7-5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95% CI 1.4-5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95% CI 1.2-4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95% CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95% CI 0.42-0.85).
Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.
塔帕辛是主要组织相容性复合体（MHC）I类抗原呈递途径的关键组成部分。该途径的缺陷可导致肿瘤免疫逃逸。本研究的目的是检测塔帕辛表达是否与结直肠癌（CRC）中CD8(+)细胞毒性T淋巴细胞（CTL）浸润及总生存期相关。
本研究纳入了198例具有完整临床病理信息的CRC患者的下一代组织微阵列（ngTMA）。TMA载玻片进行塔帕辛、MHC I和CD8免疫染色。分析标志物表达与免疫细胞浸润、患者生存期及TNM分期的关系。
塔帕辛表达降低与静脉侵犯（AUC 0.682，OR 2.7，p = 0.002；95%CI 1.7 - 5.0）、淋巴侵犯（AUC 0.620，OR 2.0，p = 0.005；95%CI 1.3 - 3.3）、远处转移（AUC 0.727，OR 2.9，p = 0.004；95%CI 1.4 - 5.9）及浸润性肿瘤边界形态（AUC 0.621，OR 2.2，p = 0.017；95%CI 1.2 - 4.4）密切相关。此外，塔帕辛表达与CD8(+) CTL浸润（AUC 0.729，OR 5.4，p < 0.001；95%CI 2.6 - 11）及良好的总生存期（p = 0.004，HR 0.6，95%CI 0.42 - 0.85）相关。
已发表的功能数据表明塔帕辛促进抗原呈递以及CD8(+) CTL对肿瘤的免疫识别和破坏，与此一致，塔帕辛表达降低与CRC肿瘤进展相关。
