The localization and density of immunecells in primary tumors of human metastatic colorectal cancer showsan association with response to chemotherapy

摘要

In situ immunohistochemical staining of tumor-infiltrating immune cells in large cohorts of human colorectal cancers has recently supported the hypothesis that the adaptive immune response influences the behavior of human tumors. Tumor-infiltrating immune cells therefore represent a valuable prognostic marker for patients with colorectal cancer, with a high density of immune cells being associated with a good outcome independently of other established prognostic markers. The aim of the present study was to investigate the correlation between infiltrates of immune cells, in either the primary tumor or (where available) the corresponding liver metastases, with the response to chemotherapy in patients with metastatic colorectal cancer. The analysis consisted of 32 samples from 22 patients with metastasized colorectal cancer, including ten pairs of primary tumors and corresponding liver metastases. In primary tumors the ratio of stained immune cells in the epithelial portion of the tumor as compared to the total number of immune cells staining for CD3, CD8 and Granzyme B showed a relationship to the response to chemotherapyand the time to progression under chemotherapy. The primary tumorsshowed marked intra-tumoral heterogeneity with respect to immunecell densities. Infiltrate densities differed significantly betweencorresponding primary tumors and liver metastases, a variabilitythat was also observed at the invasive margin of liver metastases.This suggests that immune infiltrates at the invasive margin ofliver metastases could be predictive with respect to response totreatment. This is currently being evaluated in a larger patientcohort.