Augmentation of the generation of cytotoxic T lymphocytes against syngeneic tumor cells by recombinant human tumor necrosis factor

Nakano, K; Okugawa, Kenji; Furuichi, Hatsuo; Y, Matsui; Sohmura, Yasunobu

doi:10.1016/0008-8749(89)90183-4

Cited by 17 publications

(3 citation statements)

References 21 publications

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“…Since TNF‐α and IL‐1α are known potent activators of host anti‐tumor cells (Palladino et al, 1987; Nakano et al, 1989), immuno‐histochemical studies were performed on tumor tissues from control (groups 1, 2 and 3) and experimental (group 4) animals for infiltrating macrophages and T cells. It was found that in tumors from animals receiving HSV‐tk and GCV treatment (group 4) there was a significant increase in macrophages (4%) and T cells ( p = 1.8%) as compared with control animals (groups 1, 2 and 3).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of tumor killing using a combination of tumor immunization andHSV-tk suicide gene therapy

et al. 1999

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Tumor cells genetically modified with the herpes simplex virus thymidine kinase (HSV‐tk) gene in combination with ganciclovir (GCV) demonstrate a “bystander effect”. Previous attempts to enhance the bystander tumor killing by combining cytokine genes with HSV‐tk/GCV have met with varying results. The present study was designed to determine the effects of tumor immunization in combination with HSV‐tk gene‐modified tumor cells and GCV on tumor killing and to determine if the bystander tumor killing could be enhanced. Tumor‐bearing mice immunized with syngeneic tumor (KBALB) prior to treatment with an i.p. injection of xenogeneic HSV‐tk gene‐modified tumor cells (PA‐1STK) had prolonged animal survival (group 4, 56.4 days). In contrast, unimmunized tumor‐bearing mice (group 2) or tumor‐bearing mice immunized to the xenogeneic PA‐1STK tumor cells (group 5) showed a mean survival of about 27 days after receiving an i.p. injection of PA‐1STK cells and GCV. Control groups, which were either not immunized and did not receive HSV‐tk cells (group 1) or immunized but treated only with GCV (group 3) showed short survival (16–18 days). Analysis of tumors for cytokine mRNA expression revealed increased TNF‐α and IL‐1α mRNA expression in group 4 mice. Furthermore, IL‐2 mRNA expression was detectable on days 2 and 4 only in group 4 mice. Immunophenotypic analysis for tumor‐infiltrating lymphocytes demonstrated an increase in macrophage (4%, p = 0.0001) and T cells (1.8%, p < 0.001) in group 4 mice with an enhanced T‐cell response as compared with mice from groups 1, 2 and 3. Our results demonstrate that tumor immunization combined with HSV‐tk/GCV treatment results in increased animal survival with enhanced immune response. Furthermore, the cytokine milieu observed in the present study can modulate the tumor micro‐environment in vivo from one that is immunosuppressive to one that is immune‐stimulatory. Int. J. Cancer 80:380–386, 1999. © 1999 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Enhancement of tumor killing using a combination of tumor immunization andHSV-tk suicide gene therapy

et al. 1999

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“…Furthermore, TNF-alpha either alone or in combination with IL-2 has been demonstrated to increase the generation of specific cytotoxic T lymphocytes (Nakano et al, 1989;Whiteside et al, 1989). Since the function, but not the toxicity, of these two molecules is synergistic, this piece of information may be clinically adapted to improve the safety and to achieve therapeutic efficacy of immunotherapy trials without appreciable toxicity.…”

Section: Diseases In Which An Increase Of Tnf Has Been Foundmentioning

confidence: 99%

Tumour necrosis factor: a cytokine with multiple biological activities

Semenzato

1990

Br J Cancer

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“…It has been shown to enhance cytotoxicity of CD8 ϩ T cell subsets and natural killer cells [6,7], to stimulate proliferation of thymocytes and mature T cells in the presence of suboptimal doses of mitogenic lectins, e.g., phytohemagglutinin or concanavalin A (Con A) [8 -10], and to costimulate T cell proliferation together with other cytokines such as IL-2 [11]. TNF-␣ sustains proliferation in Staphylococcus aureus Cowan-activated B cells and costimulates with anti-the induction of B cell DNA synthesis [12].…”

Section: Introductionmentioning

confidence: 99%

Regulation of TCR-mediated T cell activation by TNF-RII

Aspalter¹,

Eibl²,

Wolf³

2003

Journal of Leukocyte Biology

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In the present study, we investigated the role of tumor necrosis factor receptor II (TNF-RII) in human T cell activation induced via the T cell receptor (TCR) in an antigen-presenting cell-independent system. Our results confirm that interaction of TNF-alpha with TNF-RII but not TNF-RI is directly costimulatory to TCR-mediated T cell activation, thereby augmenting T cell proliferation, expression of T cell activation markers (CD25, human leukocyte antigen-DR, TNF-RII), and secretion of cytokines such as interferon-gamma and TNF-alpha. In contrast to the well-defined costimulatory molecule CD28, costimulation via TNF-RII showed significant differences in kinetics, requirement for cross-linking, redundancy of intracellular signaling pathways involved, and the capacity to induce interleukin (IL)-2, IL-10, and IL-13 secretion. In addition, cross-linking TNF-RII had the capacity to down-regulate TCR/CD28-induced Ca++ mobilization, IL-2 mRNA expression, and IL-2 and IL-10 secretion. Taken together, our findings demonstrate that TNF-RII plays a unique role among the T cell costimulatory molecules, as TNF-RII ligation can have positive and negative effects on TCR-dependent signaling. TNF-RII cross-linking has an inhibitory effect on early TCR signaling events proximal to induction of Ca++ flux, which ultimately leads to modulation of the T cell cytokine pattern expressed.

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Augmentation of the generation of cytotoxic T lymphocytes against syngeneic tumor cells by recombinant human tumor necrosis factor

Cited by 17 publications

References 21 publications

Enhancement of tumor killing using a combination of tumor immunization andHSV-tk suicide gene therapy

Enhancement of tumor killing using a combination of tumor immunization andHSV-tk suicide gene therapy

Tumour necrosis factor: a cytokine with multiple biological activities

Regulation of TCR-mediated T cell activation by TNF-RII

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