Down-regulation of the antigen processing machinery is linked to a loss of inflammatory response in colorectal cancer

作者：Kasajima Atsuko; Sers Christine; Sasano Hironobu; Johrens Korinna; Stenzinger Albrecht; Noske Aurelia; Buckendahl Ann Christin; Darb Esfahani Silvia; Mueller Berit Maria; Budczies Jan; Lehman Annika; Dietel Manfred; Denkert Carsten; Weichert Wilko^*

来源：Human Pathology, 2010, 41(12): 1758-1769.

DOI：10.1016/j.humpath.2010.05.014

• Colorectal cancer
• Transporters associated with antigen processing
• Major histocompatibility complex
• Inflammation
• Prognosis

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 1 antigen expression (TAP1 r = 0363, P < 001, TAP2 r = 0393, 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 colorecta

• 出版日期2010-12