Polarization of Tumor Infiltrating Leukocytes from Innate Immunity and their role in the Pro-angiogenic Phenotype in NSCLC

Non-small cell lung cancer (NSCLC), the most frequent lung cancer (80%), can be phenotypically classified into\udtwo main subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (ADC). While SCC has relatively rapid\uddoubling times from the onset, ADC has longer doubling times initially that become reduced during tumor\udprogression, suggesting a key role for the microenvironment. During lung tumor progression, a complex and\uddynamic interplay occurs between proliferating tumor cells and stromal, endothelial and immune tumor-conditioned\udhost cells within the tumor microenvironment (TUMIC). Several factors within the TUMIC, such as hypoxia, cytokines\udand soluble factors, appear to blunt the anti-tumor immune response and polarize immune cells towards a pro-tumor\udphenotype. Phenotypically and functionally altered immune cells found in cancer patients include macrophages,\udneutrophils, myeloid, dendritic, and even NK cells. We studied tumor infiltrating (TINK) and tumor associated (TANK)\udNK cells in NSCLC. NSCLC TINKs and TANKs show similarities to decidual NK cells, being polarized toward tissue\udbuilders, rather than killers, and producing pro-angiogenic cytokines. The functionally polarized immune cells in\udNSCLC provide the stromal support and neovascularization required for NSCLC tumor expansion and progression in\uda feed-forward mechanism, leading to tumor progression. Further, systemic alterations of immune cells are also\udpresent in NSCLC patients. The precise knowledge of these immune cell alterations within the TUMIC has become\udcrucial for diagnosis, targeted therapeutic intervention, as well as prevention, of NSCLC cancer