title: The localization and density of immune cells in primary tumors of human metastatic colorectal cancer shows an association with response to chemotherapy.
abstract: 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 chemotherapy and the time to progression under chemotherapy. The primary tumors showed marked intra-tumoral heterogeneity with respect to immune cell densities. Infiltrate densities differed significantly between corresponding primary tumors and liver metastases, a variability that was also observed at the invasive margin of liver metastases. This suggests that immune infiltrates at the invasive margin of liver metastases could be predictive with respect to response to treatment. This is currently being evaluated in a larger patient cohort.
authors.affiliation: Medical Oncology, National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.forename: Sara
authors.initials: S
authors.lastname: Michel
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Inka
authors.initials: I
authors.lastname: Zoernig
authors.forename: Thora
authors.initials: T
authors.lastname: Pommerencke
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Niels
authors.initials: N
authors.lastname: Grabe
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000556:secondary*; D008214:Lymphocytes / Q000276:immunology; D009361:Neoplasm Invasiveness; D012016:Reference Values
chemical_list: D017252:CD3 Complex; D016827:CD8 Antigens; D053804:Granzymes