Pathophysiologic significance of host reactions in human cancer tissue: desmoplasia and tumor immunity

Abstract

Invasive growth of malignant cells, particularly carcinoma cells, induces host reaction within and around tumor tissue. Representatives of them are desmoplasia, angiogenesis and immune reactions. Desmoplasia, a process of fibrosis, is induced by activation of fibroblasts with increased production of matrix proteins and matrix degrading enzymes. Angiogenesis is prerequisite for the growth of solid tumor. Inhibition of this is now a target of cancer therapy. The present author has proposed a concept that tumor vessels are composed of nutrient vessels and immune/inflammatory vessels. The latter is similar to venules in inflammatory lesions expressing the cell adhesion molecules to facilitate the transmigration of inflammatory cells to the tissue. In colon cancer, venules distributed along the invasive margin correspond to these vessels, which express E-, and P-selectins, and ICAM-1. These venules are considered to be an entry site of immune/inflammatory cells to cancer tissue. To further analyze immune mechanism, the present authors have confirmed that macrophages distributed along the invasive margin of colon cancer express costimulatory molecules B7.1/B7.2, which are required for the proliferation of T-cells. T-cells were co-localized with these cells. Clinicopathologic analysis confirmed that CD8+ T-cells distributed within cancer cell nest (intraepithelial) have the most significant impact on the patients' survival in colorectal cancer. These data suggest that various host reactions take place in the stroma of cancer tissue, which modulate the biologic behavior of cancer.