title: Down-regulation of the antigen processing machinery is linked to a loss of inflammatory response in colorectal cancer.
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.
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasajima
authors.forename: Christine
authors.initials: C
authors.lastname: Sers
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Korinna
authors.initials: K
authors.lastname: Jöhrens
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Buckendahl
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Annika
authors.initials: A
authors.lastname: Lehman
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D003106:Colon / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012007:Rectum / Q000473:pathology / Q000601:surgery
chemical_list: D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C477327:transporter associated with antigen processing (TAP)