The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown.
Dr Franck Pagès and colleagues studied pathological signs of early metastatic invasion in 959 specimens of resected colorectal cancer.
The local immune response within the tumor was studied by flow cytometry, low-density-array real-time polymerase-chain-reaction assay, and tissue microarrays.
Univariate analysis showed differences in disease-free according to the presence or absence of histologic signs of early metastatic invasion.
The investigators also found differences in overall survival according to the presence or absence of histologic signs of early metastatic invasion.
| The tumors differed in the levels of expression of 65 combinations of T-cell markers|
|New England Journal of Medicine|
Multivariate Cox analysis showed that an early conventional pathological tumor-node-metastasis stage was independently associated with increased survival.
In addition, the team found that absence of early metastatic invasion was independently associated with increased survival.
The investigators compared tumors with signs of early metastatic invasion.
Tumors without such signs had increased infiltrates of immune cells and increased levels of messenger RNA for products of type 1 helper effector T cells.
The team observed that these tumors also had increased levels of interferon regulatory factor 1, interferon-, granulysin, and granzyme B.
However, the team noted that these tumors did not have increased levels of inflammatory mediators or immunosuppressive molecules.
The 2 types of tumors had significant differences in the levels of expression of 65 combinations of T-cell markers.
Hierarchical clustering showed that markers of T-cell migration, activation, and differentiation were increased in tumors without signs of early metastatic invasion.
The latter type of tumors also had increased numbers of CD8+ T cells, ranging from early memory to effector memory T cells.
The investigators evaluated levels of infiltrating memory CD45RO+ immunohistochemically.
The team found that high levels of these memory cells correlated with a less advanced pathological stage, and increased survival.
Dr Pagès' team commented, “Signs of an immune response within colorectal cancers are associated with the absence of pathological evidence of early metastatic invasion and with prolonged survival.”