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

Atsuko Kasajima, Christine Sers, Hironobu Sasano, Korinna Jöhrens, Albrecht Stenzinger, Aurelia Noske, Ann Christin Buckendahl, Silvia Darb-Esfahani, Berit Maria Müller, Jan Budczies, Annika Lehman, Manfred Dietel, Carsten Denkert, Wilko Weichert

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1758-1769
Number of pages12
JournalHuman Pathology
Volume41
Issue number12
DOIs
Publication statusPublished - 2010 Dec

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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