Tumor MHC Class I Expression Improves the Prognostic Value of T-cell Density in Resected Colorectal Liver Metastases

Using a tissue microarray of liver metastases from 158 patients with colorectal cancer, Turcotte and colleagues show that high MHC class I expression with dense intratumoral T-cell infiltration identifies patients with favorable outcomes independent of conventional prognostic factors. Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM) have been associated with more favorable patient outcomes, but whether MHC class I (MHC-I) expression on cancer cells affects prognosis is uncertain. Immunohistochemistry was performed on a tissue microarray of 158 patients with CLM, who underwent partial hepatectomy with curative intent. Using the antibody HC-10, which detects HLA-B and HLA-C antigens and a minority of HLA-A antigens, MHC-I expression was correlated with β-2 microglobulin (β2m; r = 0.7; P < 0.001), but not with T-cell density (r < 0.32). The median follow-up for survivors was 9.7 years. High levels of MHC-I expression in tumors concomitant with high T-cell infiltration (CD3, CD4, or CD8) best identified patients with favorable outcomes, compared with patients with one or none of these immune features. The median overall survival (OS) of patients with MHC-IhiCD3hi tumors (n = 31) was 116 months compared with 40 months for the others (P = 0.001), and the median time to recurrence (TTR) was not reached compared with 17 months (P = 0.008). By multivariate analysis, MHChiCD3hi was associated with OS and TTR independent of the standard clinicopathologic variables. An immune score that combines MHC-I expression and TIL density may be a valuable prognostic tool in the treatment of patients with CLM. Cancer Immunol Res; 2(6); 530–7. ©2014 AACR.

[1]  M. Gonen,et al.  Regulatory T Cell Infiltration Predicts Outcome Following Resection of Colorectal Cancer Liver Metastases , 2013, Annals of Surgical Oncology.

[2]  F. Marincola,et al.  Cancer classification using the Immunoscore: a worldwide task force , 2012, Journal of Translational Medicine.

[3]  C. Sautès-Fridman,et al.  The immune contexture in human tumours: impact on clinical outcome , 2012, Nature Reviews Cancer.

[4]  Axel Benner,et al.  Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. , 2011, Cancer research.

[5]  Laurence Zitvogel,et al.  Immune parameters affecting the efficacy of chemotherapeutic regimens , 2011, Nature Reviews Clinical Oncology.

[6]  Zlatko Trajanoski,et al.  Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  W. Weichert,et al.  Down-regulation of the antigen processing machinery is linked to a loss of inflammatory response in colorectal cancer. , 2010, Human pathology.

[8]  M. Ilyas,et al.  Intratumoral T cell infiltration, MHC class I and STAT1 as biomarkers of good prognosis in colorectal cancer , 2010, Gut.

[9]  H. Putter,et al.  The Predictive Value of HLA Class I Tumor Cell Expression and Presence of Intratumoral Tregs for Chemotherapy in Patients with Early Breast Cancer , 2010, Clinical Cancer Research.

[10]  K. Zatloukal,et al.  In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  M. Gonen,et al.  T Cell Infiltrate Predicts Long-Term Survival Following Resection of Colorectal Cancer Liver Metastases , 2009, Annals of Surgical Oncology.

[12]  Yuman Fong,et al.  Actual 10-year survival after resection of colorectal liver metastases defines cure. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  Z. Trajanoski,et al.  Type, Density, and Location of Immune Cells Within Human Colorectal Tumors Predict Clinical Outcome , 2006, Science.

[14]  Z. Trajanoski,et al.  Effector memory T cells, early metastasis, and survival in colorectal cancer. , 2005, The New England journal of medicine.

[15]  G. Maddern,et al.  The clinical risk score: emerging as a reliable preoperative prognostic index in hepatectomy for colorectal metastases. , 2004, Archives of surgery.

[16]  F. Garrido,et al.  Distribution of HLA class I altered phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21 , 2004, Immunogenetics.

[17]  F. Dammacco,et al.  β2-Microglobulin-Free HLA Class I Heavy Chain Epitope Mimicry by Monoclonal Antibody HC-10-Specific Peptide1 , 2003, The Journal of Immunology.

[18]  Torsten Hothorn,et al.  On the Exact Distribution of Maximally Selected Rank Statistics , 2002, Comput. Stat. Data Anal..

[19]  M. A. Sáez,et al.  The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma , 1997, Cancer.

[20]  H. Ploegh,et al.  HLA-A- and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. , 1990, International immunology.

[21]  H. Ljunggren,et al.  Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy , 1986, Nature.

[22]  Carsten Denkert,et al.  Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  F. Garrido,et al.  MHC class I antigens and immune surveillance in transformed cells. , 2007, International review of cytology.

[24]  I. Ellis,et al.  Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis , 2006, International journal of cancer.

[25]  H. Ljunggren,et al.  In search of the 'missing self': MHC molecules and NK cell recognition. , 1990, Immunology today.