Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

• Published in: Laboratory investigation Vol. 84; no. 4; pp. 493 - 501
• Main Authors: Menon, Anand G, Janssen - van Rhijn, Connie M, Morreau, Hans, Putter, Hein, Tollenaar, Rob A E M, van de Velde, Cornelis J H, Fleuren, Gert Jan, Kuppen, Peter J K
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2004; Nature Publishing; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biotechnology; CD57 Antigens - analysis; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - pathology; extracellular matrix protein; Female; Fundamental and applied biological sciences. Psychology; HLA-A Antigens - analysis; HLA-B Antigens - analysis; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Leukocytes - physiology; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical sciences; microsatellite instability; Microsatellite Repeats; Middle Aged; natural killer cells; Prognosis; T-Lymphocytes, Cytotoxic - immunology; tumor-infiltrating leukocytes; natural killer cells; microsatellite instability; extracellular matrix protein; colorectal cancer; prognosis; tumor-infiltrating leukocytes; Immunohistochemistry; Biotechnology; Rectal disease; Biochemical analysis; Prognosis; Colorectal cancer; Malignant tumor; Colonic disease; Anatomic pathology; Clinical biology; Digestive diseases; Intestinal disease; Immune system
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700055

The efficacy of tumor cell–immune cell interactions depends on a number of factors, for example, the expression of HLA-I on tumor cells, the type of immune cell, the accessibility of tumor cells for immune cells and the expression of immunogenic epitopes. We assessed infiltration of CD4+, CD8+, CD56+ and CD57+ cells in the tumor epithelium, tumor stroma and advancing tumor margin of 93 colorectal carcinomas and correlated this to clinicopathological parameters, the expression of HLA-A and HLA-B/C on tumor cells, the presence of a basal membrane (BM)-like structure surrounding tumor nodules and the presence of microsatellite instability/mutator phenotype (absent MLH-1 expression). The median intraepithelial CD4+, CD8+, CD56+ and CD57+ cell infiltrations were 3, 23, 0 and 0 cells/mm2 tumor, respectively. HLA-A/BC expression by tumor cells was normal in 28/43%, heterogeneous in 59/48% and absent in 13/9% of the cases. A BM-like structure surrounding the tumor nodules was absent, present and thick in 47, 38 and 15% of the cases. Six cases lost MLH1 expression. There was a positive correlation between leukocyte infiltration in the three compartments for CD4+, CD8+, CD56+ (partly) and CD57+ (all P<0.05) cell infiltration. Intraepithelial CD8+ cell infiltration inversely correlated with HLA-A (P=0.04) and HLA-B/C expression (P=0.04). Intraepithelial CD57+ cell infiltration inversely correlated with HLA-B/C expression (P=0.04). Moreover, intraepithelial infiltration of CD8+ and CD57+ cells was inversely correlated to the presence of a BM-like structure (P=0.003 and 0.04, respectively). Uni- and multivariate analyses showed that a lower tumor stage (P=0.004) and marked infiltration of CD8+ (P=0.04) and CD57+ cells (P=0.05) at the advancing tumor margin were independent prognostic factors for a longer disease-free survival. Loss of MLH1 expression was correlated with a significantly higher intraepithelial CD8+ and CD57+ cell infiltration. We conclude that infiltration of CD8+ and CD57+ cells are important prognostic factors in colorectal cancer. However, their interaction with tumor cells is inversely correlated to the presence of HLA-I on tumor cells and a thick BM-like structure around tumor islets. Our data indicate that NK cells might play an important role in the immune surveillance in colorectal cancer patients.