Differential impact of tumor-infiltrating immune cells on basal and luminal cells: Implications for tumor invasion and metastasis

Background/Aim: Regarding the impact of tumor-infiltrating immune cells on tumor cells, many contradictory reports have been published. We have hypothesized that these controversies result from differences in tissue types and tumor stages, in which immune cells are variably distributed and differentially associated with epithelial cells. Our current study compared the pattern and frequency of physical association of tumor-infiltrating immune cells with different parenchymal cells of human breast and prostate tumors harboring normal, hyperplastic, in situ, and invasive components. Materials and Methods: The cytological, biological, and molecular alterations were assessed with double immunohistochemistry, double fluorescent labeling, apoptosis assay, and gene expression profiling. Results: Our study detected several previously undescribed features: (i) over 95% of infiltrating immune cells were seen within normal, hyperplastic, or in situ cancer structures with focally-disrupted capsules, and fewer than 5% were found within invasive cancer; (ii) over 95% of normal, hyperplastic, and in situ cancerous epithelial cells were physically shielded from immune cells by the surrounding myoepithelial or basal cell layer; (iii) about 90% of myoepithelial or basal cells physically associated with immune cells and such residual cells within focally disrupted layers exhibited distinct degeneration, including apoptosis, necrosis, and reduced expression of tumor suppressor p63; (iv) epithelial cells overlying focally disrupted tumor capsules surrounded by immune cells had substantially higher proliferation than their adjacent counterparts, and some of the proliferating cells were arranged as tongue-like projections invading the stroma; and (v) microdissected cells overlying focally disrupted tumor capsules had more than 5-fold higher expression of stem cell lineage markers KIT and NCOR2. Conclusion: Tumorinfiltrating immune cells are primarily associated with degenerated myoepithelial or basal cells causing focal disruptions of the capsule, which selectively favor proliferation, invasion, and dissemination of the overlying tumor stem cells.