We demonstrated that both EGF and TNFα were highly expressed in HCCs, and HCCs with higher expression of both EGF and TNFα were more frequently rated as high-grade tumors.
We could now demonstrate that Gli2 gene silencing in BCC tissues made the tumor sensitive to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-mediated cell death by downregulating cFlip.
We conclude that the stromal elements of ovarian tumors express MMP-2 and 9 and their specific inhibitors, but these do not seem to be controlled by endogenous TNF in the tumor microenvironment.
We assessed TIL expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), granulocyte-macrophage colony stimulating factor (GM-CSF), IL-10, and transforming growth factor-beta (TGF-beta), and tumor cell expression of IL-10 and TGF-beta in situ in 49 primary colon carcinomas and 20 metastases using immunohistochemistry.
Viruses or virally infected cells (including tumor cells) induce the production of lymphokines and cytokines (interferons, interleukins and tumor necrosis factor) and activate NK cells and specific immune T cells cytotoxic to virus-infected cells (including tumor cells).7.
Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells.
Using this approach, the median survival of tumor bearing nude mice was prolonged by the administration of a human tumor necrosis factor-alpha (TNF-alpha) gene inserted into a eukaryotic strong expression vector (pcagTNF-alpha) and exogenously added interferon-gamma (INF-gamma) (72 +/- 3 days: mean +/- s.e.).
Using a mouse model of ovarian cancer in which either TNF receptor 1 (TNFR1) signaling was manipulated in different leukocyte populations or TNF-alpha was neutralized by antibody treatment, we found that this inflammatory cytokine maintained TNFR1-dependent IL-17 production by CD4+ cells and that this led to myeloid cell recruitment into the tumor microenvironment and enhanced tumor growth.
Upon treatment of tumor bearing mice significant anti-tumoral effects, an increase in TNFα as well as activation of TNFα-specific downstream signaling were evident in the BON tumor model while no comparable effects were detectable for NCI-H295R.
TWEAK, a new member of the tumor necrosis factor (TNF) family, induces cell death in some tumor cell lines, but its physiological functions are largely unknown.
Tumor-infiltrating CD45RA<sup>-</sup>CCR7<sup>-</sup> Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR. Gastric tumor-derived TNF-α induced CD45RA<sup>-</sup>CCR7<sup>-</sup> Treg subset with similar phenotype to their status in tumors and inhibited their HLA-DR expression via activating STAT3 phosphorylation.
Tumor vasculature-targeted recombinant mutated human TNF-α enhanced the antitumor activity of doxorubicin by increasing tumor vessel permeability in mouse xenograft models.
Treatment of established tumor is associated with ICAM-1 upregulation and reversed by CD8 depletion in a tumor necrosis factor-alpha gene transfected mouse mammary tumor.
Treatment of tumor cell--pre-exposed monocytes with hyaluronidase (HAase) improved their depressed production of TNF, while HAase-treated cancer cells did not cause monocyte dysfunction.
Translation of the fundamental mechanisms of TNF superfamily is leading to the design of therapeutics that can alter pathogenic processes in several autoimmune diseases or promote immunity to tumors.
Transgene expression of alpha tumor necrosis factor with mutations D142N and A144R under control of human telomerase reverse transcriptase promoter eradicates well-established tumors and induces long-term antitumor immunity.
TRAIL is a member of the tumor necrosis factor superfamily that induces apoptosis in a variety of tumor cell types both in vitro and in vivo, while demonstrating minimal cytotoxicity toward normal tissues.
TRAIL (TNF-related apoptosis-inducing ligand) is a member of the tumor necrosis factor superfamily that can induce tumor selective death by up-regulating death receptor 4 (DR4) and DR5 expression.
Together, these results suggest that TNF-enhanced tk gene therapy should provide a useful treatment for TNF-alpha-sensitive tumors and perhaps also for TNT-alpha-resistant tumors if vector delivery can be improved to increase the percentage of transduced tumor cells.
Together, our results implicate USP2 as a novel positive regulator of TNF-α-induced NF-κB signaling and show that its expression is altered in tumor cells.
To this end, in this study, we determined combination effects of anti-PD immunotherapy and oncolytic adenoviral vector-mediated tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) gene therapy (Ad/E1-TRAIL) or adenoviral-mediated TP53 (Ad/CMV-TP53) gene therapy in syngeneic mice bearing subcutaneous tumors derived from M109 lung cancer cells.