Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany.
Hum Pathol. 2010 Dec;41(12):1758-69. doi: 10.1016/j.humpath.2010.05.014.
Antitumor inflammatory response is known to inhibit tumor growth in colorectal carcinoma. The density and functionality of tumor-infiltrating lymphocytes (TIL) is regulated by the antigen processing machinery through regulator proteins such as transporters associated with antigen processing (TAP) and major histocompatibility complex (MHC) class I antigen. We aimed to investigate the in vivo association of those factors and their impact on prognosis in colorectal cancer. TAP1, TAP2 and MHC class I antigen expression, inflammatory infiltrate and TIL (CD4(+), CD8(+), and CD20(+)) were assessed by immunohistochemistry in 336 sporadic colorectal carcinomas. The factors were correlated with each other and with clinic-pathological parameters and patient outcome. We found TAP1 and TAP2 expression to be significantly associated with MHC class I antigen expression (TAP1: r = 0.363, P < .001; TAP2: r = 0.393, P < .001). Increased density of CD8(+) TIL was predominantly found in TAP1, TAP2 and MHC class I antigen-positive cases. Increased density of CD4(+) TIL was linked with TAP1 and TAP2, but not with MHC class I antigen. High CD4(+) and CD8(+) cell count but not TAP1, TAP2 and MHC class I antigen expression had favorable prognostic impact in colorectal cancer (P = .003 and P = .003, respectively). In conclusion, our data show that the expression of key components of the antigen processing machinery is tightly linked to the density of TIL, which are positive prognostic factors in colorectal cancer in vivo. This implies that modulation of these factors may help to enhance antitumor inflammatory response which in turn may improve patient prognosis.
抗肿瘤炎症反应已知可抑制结直肠癌中的肿瘤生长。肿瘤浸润淋巴细胞（TIL）的密度和功能受抗原加工机制通过调节蛋白（如抗原加工相关转运蛋白（TAP）和主要组织相容性复合体（MHC）I 类抗原）调节。我们旨在研究这些因素的体内相关性及其对结直肠癌预后的影响。在 336 例散发性结直肠癌中，通过免疫组织化学评估 TAP1、TAP2 和 MHC I 类抗原表达、炎症浸润和 TIL（CD4(+)、CD8(+)和 CD20(+)）。这些因素与彼此以及与临床病理参数和患者预后相关。我们发现 TAP1 和 TAP2 表达与 MHC I 类抗原表达显著相关（TAP1：r = 0.363，P <.001；TAP2：r = 0.393，P <.001）。CD8(+)TIL 的密度增加主要见于 TAP1、TAP2 和 MHC I 类抗原阳性病例。CD4(+)TIL 的密度增加与 TAP1 和 TAP2 相关，但与 MHC I 类抗原无关。高 CD4(+)和 CD8(+)细胞计数而非 TAP1、TAP2 和 MHC I 类抗原表达对结直肠癌具有有利的预后影响（P =.003 和 P =.003）。总之，我们的数据表明，抗原加工机制的关键组成部分的表达与 TIL 的密度紧密相关，TIL 是结直肠癌体内的预后良好因素。这意味着这些因素的调节可能有助于增强抗肿瘤炎症反应，从而可能改善患者的预后。
