Loss of tapasin correlates with diminished CD8+ T-cell immunity and prognosis in colorectal cancer

被引:40
作者
Sokol, Lena [1 ]
Koelzer, Viktor H. [1 ,2 ]
Rau, Tilman T. [1 ,2 ]
Karamitopoulou, Eva [1 ,2 ]
Zlobec, Inti [1 ]
Lugli, Alessandro [1 ,2 ]
机构
[1] Univ Bern, TRU, Inst Pathol, CH-3010 Bern, Switzerland
[2] Univ Bern, Clin Pathol Div, Inst Pathol, CH-3010 Bern, Switzerland
关键词
Colorectal cancer; Prognostic factor; Immune infiltration; Tapasin; MHC I; Antigen presentation; CD8; Cytotoxic lymphocytes; Immune activation; Immunosurveillance; MHC CLASS-I; TUMOR MICROENVIRONMENT; PEPTIDE BINDING; DOWN-REGULATION; EXPRESSION; CARCINOMA; MOLECULES; SURVIVAL; MECHANISMS; INCREASES;
D O I
10.1186/s12967-015-0647-1
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival. Methods: A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging. Results: A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95 % CI 1.7-5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95 % CI 1.4-5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95 % CI 1.2-4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95 % CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95 % CI 0.42-0.85). Conclusions: Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.
引用
收藏
页数:6
相关论文
共 27 条
[1]   Mhc class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma [J].
Atkins, D ;
Breuckmann, A ;
Schmahl, GE ;
Binner, P ;
Ferrone, S ;
Krummenauer, F ;
Strökel, S ;
Seliger, B .
INTERNATIONAL JOURNAL OF CANCER, 2004, 109 (02) :265-273
[2]   Differential contribution of TAP and tapasin to HLA class I antigen expression [J].
Belicha-Villanueva, Alan ;
McEvoy, Sarah ;
Cycon, Kelly ;
Ferrone, Soldano ;
Gollnick, Sandra O. ;
Bangia, Naveen .
IMMUNOLOGY, 2008, 124 (01) :112-120
[3]   Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways:: β2-microglobulin inactivation in MSI-positive tumors and LMP7/TAP2 downregulation in MSI-negative tumors [J].
Cabrera, CM ;
Jiménez, P ;
Cabrera, T ;
Esparza, C ;
Ruiz-Cabello, F ;
Garrido, F .
TISSUE ANTIGENS, 2003, 61 (03) :211-219
[4]   Mechanisms of MHC class I-restricted antigen processing and cross-presentation [J].
Cresswell, P ;
Ackerman, AL ;
Giodini, A ;
Peaper, DR ;
Wearsch, PA .
IMMUNOLOGICAL REVIEWS, 2005, 207 :145-157
[5]   Disulfide bond isomerization and the assembly of MHC class I-Peptide complexes [J].
Dick, TP ;
Bangia, N ;
Peaper, DR ;
Cresswell, P .
IMMUNITY, 2002, 16 (01) :87-98
[6]   Downregulation of tapasin expression in progressive human malignant melanoma [J].
Dissemond, J ;
Kothen, T ;
Mörs, J ;
Weimann, TK ;
Lindeke, A ;
Goos, M ;
Wagner, SN .
ARCHIVES OF DERMATOLOGICAL RESEARCH, 2003, 295 (02) :43-49
[7]   Type, density, and location of immune cells within human colorectal tumors predict clinical outcome [J].
Galon, Jerom ;
Costes, Anne ;
Sanchez-Cabo, Fatima ;
Kirilovsky, Amos ;
Mlecnik, Bernhard ;
Lagorce-Pages, Christine ;
Tosolini, Marie ;
Camus, Matthieu ;
Berger, Anne ;
Wind, Philippe ;
Zinzindohoue, Franck ;
Bruneval, Patrick ;
Cugnenc, Paul-Henri ;
Trajanoski, Zlatko ;
Fridman, Wolf-Herman ;
Pages, Franck .
SCIENCE, 2006, 313 (5795) :1960-1964
[8]  
Garbi N, 2000, IMPAIRED IMMUNE RESP, P1
[9]   Impaired assembly yet normal trafficking of MHC class I molecules in tapasin mutant mice [J].
Grandea, AG ;
Golovina, TN ;
Hamilton, SE ;
Sriram, V ;
Spies, T ;
Brutkiewicz, RR ;
Harty, JT ;
Eisenlohr, LC ;
Van Kaer, L .
IMMUNITY, 2000, 13 (02) :213-222
[10]   HLA class I antigen processing machinery component expression and intratumoral T-cell infiltrate as independent prognostic markers in ovarian carcinoma [J].
Han, Liz Y. ;
Fletcher, Mavis S. ;
Urbauer, Diana L. ;
Mueller, Peter ;
Landen, Charles N. ;
Kamat, Aparna A. ;
Lin, Yvonne G. ;
Merritt, William M. ;
Spannuth, Whitney A. ;
Deavers, Michael T. ;
De Geest, Koen ;
Gershenson, David M. ;
Lutgendorf, Susan K. ;
Ferrone, Soldano ;
Sood, Anil K. .
CLINICAL CANCER RESEARCH, 2008, 14 (11) :3372-3379