Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: their relationship to KRAS mutational status and disease recurrence.

Department of Immunology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
 
Abstract
The prognosis of newly diagnosed colorectal cancer patients relies mostly on tumor-node metastasis classification. However, analyses of tumor-infiltrating lymphocytes and several molecular markers have also shown promising prognostic value. Mutations in the proto-oncogene KRAS, which occur early in colorectal carcinogenesis, have been demonstrated to be common in human colorectal cancer (CRC); however, their prognostic significance remains controversial. We examined the correlations between KRAS mutational status and tumor-infiltrating immune cells with respect to CRC recurrence. Mutations in KRAS were identified in 45.5% of the primary carcinomas in our cohort of patients: 65% in codon 12 and 35% in codon 13. Although codon 13 KRAS mutations were associated with disease relapse, they were present in both disease-free and relapsed patients. However, disease-free and relapsed patients differed markedly in their patterns of tumor-infiltrating immune cells. There was a trend toward decreased density of tumor-infiltrating lymphocytes (TILs) within the group of relapsed cases. In addition, relapsed patients with codon 13 mutations had markedly lower levels of tumor-infiltrating mature DC-LAMP(+) dendritic cells (DCs) and higher frequency of CD1a(+) cells compared with disease-free patients. Our data suggest that CRC patients with low levels of TILs, a high CD1a(+)/DC-LAMP(+) tumor-infiltrating DC ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence.