Unique Immunoregulation of Lung Cancer by CD8+ T Cells

Abstract We hypothesize that immunoregulation of lung cancer differs from other malignancies. To study this hypothesis in greater detail, we utilized a primary carcinogenesis model 3-MCA-induced flank fibrosarcoma or urethane-mediated B6 wild-type CD8+ T cell deficient mice. deficiency increased sarcoma tumor growth (199±65 vs. 511±138 mm 3for vs CD8−/−mice respectively p = 0.03) but decreased the (1.7±0.2 0.6±0.13 cm 0.006). validated surprising finding multiple models including B16 melanoma, EG7 lymphoma and LLC cancer. For all non-lung tumors, presence cells growth. In direct contrast, accelerated Cytokine analysis revealed significant cell-dependent increase Th-1 polarizing cytokines, IFN-γ TNF-α, cancer-bearing not melanoma-bearing Similar to deficiency, neutralization TNF-α mice ameliorated addition, noted an TNF-α-dependent expansion CD8+Foxp3+ infiltrating lymphocytes mice, Therefore, contrary accepted dogma, mediated some fashion by associated cells, facilitates rather than ameliorates malignancy. Our data suggests is unique may require novel immunomodulating strategies necessarily apply This project was funded P01 AI116501, R01 AI145108, I01BX002299