{'fraction_non_alphanumeric': 0.021304347826086957, 'fraction_numerical': 0.01217391304347826, 'mean_word_length': 5.286885245901639, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Derived from Human Solid TumorsFibroblasts Activation of T Lymphocytes and Reciprocal Functional Modulation of the

Fibroblasts are a dominant cell type in most human solid tumors. The possibility that ﬁbroblasts have the capacity to interact with and modulate the function of tumor-associated T lymphocytes makes them a potential therapeutic target. To address this question, primary cultures of ﬁbroblasts derived from human lung tumors were established and cultured with T cells derived from the same tumor. The tumor ﬁbroblasts signiﬁcantly enhance the production of IFN- g and IL-17A by the tumor-associated T cells following a CD3/CD28-induced activation of the T cells. This enhancement was ﬁbroblast cell dose-dependent and did not require direct contact between the two cell types. Tumor-associated ﬁbroblast-conditioned media similarly enhanced both IFN- g and IL-17A in activated T cells, and this enhancement was signiﬁcantly reduced by Abs to IL-6. Conditioned media derived from activated lymphocyte cultures signiﬁcantly enhanced IL-6 production by tumor ﬁbroblasts. A similar enhancement of IFN- g and IL-17A was observed when activated T cells from a normal donor were cultivated with skin ﬁbroblasts derived from the same donor. These results establish that ﬁbroblasts and autologous lymphocytes, whether derived from the tumor microenvironment or from nonmalignant tissues, have the capacity to reciprocally interact and modulate function. In contrast to other reports, ﬁbroblasts are shown to have an immunostimulatory effect upon activated T lymphocytes. The ability of ﬁbroblasts to enhance two T cell cytokines known to have an impact upon tumor progression suggests that ﬁbroblasts play an important role in tumor pathogenesis that could be exploited therapeutically. The Journal of Immunology , 2010, 185: 2681–2692. In-stitutional Review Board-approved protocols. Normal donor peripheral blood leukocytes (PBLs) were obtained from the trapped leukocytes in Trima ﬁlters from erythrocyte donors at the Roswell Park Cancer Institute pheresis facility. PBLs were depleted of granulocytes and RBCs by Ficoll density centrifugation. Monocyte depletion, when done, was accomplished by cold aggregation performed by Joseph D. Tario of the Roswell Park Flow Cytometry Facility (15).