Tumoral Downregulation of the Antigen Processing Machinery Is Tightly Linked to a Prognostically Unfavorable Loss of Inflammatory Response in Human Colorectal Carcinoma
A Kasajima, C Sers, H Sasano, K Johrens, A Stenzinger, A Noske, AC Buckendahl, S Darb-Esfahani, BM Muller, J Budczies, A Lehman, M Dietel, C Denkert, W Weichert. Charité - University of Medicine, Berlin, Germany; Tohoku University Graduate School of Medicine, Sendai, Japan
Background: Antitumor inflammatory response is known to inhibit tumor growth in colorectal carcinoma (CRC). The density and functionality of tumor infiltrating lymphocytes (TIL) in turn is regulated by the antigen presentation machinery (APM) through regulator proteins such as transporters associated with antigen processing (TAPs) and major histocompatibility complex (MHC class I) antigen. We sought to investigate the in vivo association of those factors and their impact on prognosis in colorectal cancer.
Design: TAP1, TAP2 and MHC class I expression as well as inflammatory infiltrate and TILs (CD4, CD8 and CD20) were assessed by immunohistochemistry in 336 sporadic CRCs. The factors were correlated with each other as well as with clinico-pathological parameters and patient outcome.
Results: TAP1 and TAP2 expression was significantly associated with MHC class I expression (TAP1; r = 0.363, p < 0.001, TAP2; r = 0.393, p < 0.001). Density of CD8+ TIL was predominantly found in TAP1, TAP2 and MHC class I positive cases. Density of CD4+ TIL was linked with TAP1 and TAP2, but not with MHC class I. High CD4+ and CD8+ cell count but not TAP1, TAP2 and MHC class I expression had favorable prognostic impact in colorectal cancer (p=0.003 and p=0.003, respectively).
Conclusions: Our data show that the expression of key components of the APM is tightly linked to the density of TILs, 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.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 124, Tuesday Morning