Natural cell-mediated cytotoxicity (NCMC) against NK-sensitive tumoursin vitro by murine spleen LY-6C+ natural T cells

Martiniello, R; Burton, R C; Smart, Y. C.

doi:10.1002/(sici)1097-0215(19970207)70:4<450::aid-ijc13>3.0.co;2-j

Cited by 4 publications

(1 citation statement)

References 45 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immune cells that protect the body from infection and tumour formation kill these targets using two different mechanisms: the exocytosis of cytolytic granules containing perforin and granzymes and contact‐mediated cytotoxicity involving immune cell surface ligand binding to a target cell receptor such as Fas ligand (FasL) and Fas, respectively 57. CD90 is found on the surface of cytolytic cells such as CD8 + CTL, rat spleen CD4 − CD90 high dendritic cells and a group of innate immune cells that mediate natural cell‐mediated cytotoxicity (NCMC), including murine spleen CD3 + NK1.1 + natural T cells 55, 58–61. Crosslinking of the CTL‐T cell receptor (TCR) by antigenic peptide‐MHC complexes on target cells initiates both perforin‐ and FasL‐mediated cytolysis 57.…”

Section: Discussionmentioning

confidence: 99%

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Martiniello‐Wilks

Wang

Voeks

et al. 2004

The Journal of Gene Medicine

View full text Add to dashboard Cite

Gene-directed enzyme prodrug therapy based on the E. coli purine nucleoside phosphorylase (PNP) gene produces efficient tumour cell killing. PNP converts adenosine analogs into toxic metabolites that diffuse across cell membranes to kill neighbouring untransduced cells (PNP-GDEPT). Interference with DNA, RNA and protein synthesis kills dividing and non-dividing cells, an important consideration for slow-growing prostate tumours. This study examined the impact of administering PNP-GDEPT into orthotopically grown RM1 prostate cancers (PCas) on the growth of lung pseudo-metastases of immunocompetent mice. C57BL/6 mice bearing orthotopic RM1 PCas received a single intraprostatic injection of OAdV220 (10(10) particles), a recombinant ovine atadenovirus containing the PNP gene controlled by the Rous Sarcoma virus promoter, followed by fludarabine phosphate (approximately 600 mg/m(2)/day) administered intraperitoneally (ip) once daily for 5 days. Pseudo-metastases were induced 2 days after intraprostatic vector administration by tail-vein injection of untransduced RM1 cells. Mice given PNP-GDEPT showed a significant reduction both in prostate volume (approximately 50%) and in lung colony counts (approximately 60%). Apoptosis was increased two-fold in GDEPT-treated prostates compared with controls (P < 0.01), but was absent in the lungs. Staining for proliferating cell nuclear antigen (PCNA) indicated that proliferation of both RM1 prostate tumours (P < 0.01) and lung colonies (P < 0.01) was significantly suppressed after GDEPT. Although prostate tumour immune cell infiltration did not differ significantly between treatments, immunostaining for Thy-1.2 (CD90) showed that GDEPT promoted Thy-1.2(+) cell infiltration into the prostate tumour site. This study showed that a single course of PNP-GDEPT significantly suppressed local PCa growth and reduced lung colony formation in the aggressive RM1 tumour model.

show abstract

Section: Discussionmentioning

confidence: 99%

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Martiniello‐Wilks

Wang

Voeks

et al. 2004

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

Downregulation of Innate and Acquired Antitumor Immunity by Bystander gamma delta and alpha beta T Lymphocytes with Th2 or Tr1 Cytokine Profiles

Seo

Tokura²

1999

Journal of Interferon & Cytokine Research

View full text Add to dashboard Cite

It has been thought that natural killer (NK) cells appearing early in tumor lesions play a pivotal role in the innate immunity against tumor cells. Although NK cells serve as the first tumoricidal effector cells, they subsequently promote a shift in effectors from themselves to tumor-specific cytotoxic T lymphocytes (CTLs) that mediate the acquired immunity. The mechanism of this shift has not been fully elucidated, however, NK cell-derived T helper (Th) 1 cytokines such as interferon (IFN)-gamma seem to play a key role. Another NK-lineage, termed natural killer T (NK T) cells, may also participate in the innate period when they acquire the ability to secrete Th1 cytokines. Interleukin-4 (IL-4) and IL-10, belonging to Th2, and transforming growth factor-beta (TGF-beta), belonging to T regulatory (Tr) 1 cytokines, are known to suppress the development of NK, NK T cells, as well as CTLs and to block Th0 cell differentiation to Th1 cells, suggesting that tumor cells can evade the innate and acquired immunity by virtue of cells producing these inhibitory cytokines. In early tumor lesions of murine B16 melanoma, gammadelta T and alphabeta intermediate (int) T cells that co-infiltrate with NK and NK T cells can produce Th2 cytokines and inhibit the innate immunity. In MM2 mammary tumor-bearing mice, gammadelta T cells appearing both lesionally and systemically secrete Tr1-type cytokines and depress the acquired immunity. These Th2- or Tr1-type gammadelta T and alphabeta(int) T cells downregulate the tumoricidal cells by means of both their secreted cytokines and express major histocompatibility complex (MHC) class I molecules.

show abstract

T Cell-Mediated, IFN-γ-Facilitated Rejection of Murine B16 Melanomas

Böhm

Thoma

Leithäuser

et al. 1998

The Journal of Immunology

116

View full text Add to dashboard Cite

The murine melanoma cell line B16.F10 (H-2b) was used to study specific T cell responses that reject tumors. Stable B16 transfectants were established that express viral Ags, either the hepatitis B surface Ag (HBsAg) or the large tumor Ag (T-Ag) of SV40. B16 cells and their transfected sublines were CD40+CD44+ but expressed no (or low levels of the) costimulator molecules CD154 (CD40L), CD48, CD54, CD80, and CD86. Surface expression of MHC class I (Kb, Db) and class II (I-Ab) molecules by B16 cells was low, but strikingly up-regulated by IFN-γ. CD95 (Fas) and CD95 ligand (CD95L (FasL)) were “spontaneously” expressed by B16 cells growing in vitro in serum-free medium; these markers were strikingly up-regulated by IFN-γ. B16 cells coexpressing CD95 and CD95L were irreversibly programed for apoptosis. In vitro, noninduced B16 transfectants stimulated a specific IFN-γ release response, but no cytolytic response (in a 4-h assay) in MHC class I-restricted CTL; in contrast, IFN-γ-induced B16 targets were efficiently and specifically lysed by CTL. In vivo, B16 transfectants were specifically rejected by DNA-vaccinated syngeneic hosts through a T-dependent immune effector mechanism. The tumors showed evidence of massive apoptosis in vivo during the rejection process. The data suggest that CTL-derived IFN-γ enhances an intrinsic suicide mechanism of these tumor cells in addition to facilitating lytic interactions of effectors with tumor targets.

show abstract

Natural cell-mediated cytotoxicity (NCMC) against NK-sensitive tumoursin vitro by murine spleen LY-6C+ natural T cells

Cited by 4 publications

References 45 publications

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Purine nucleoside phosphorylase and fludarabine phosphate gene‐directed enzyme prodrug therapy suppresses primary tumour growth and pseudo‐metastases in a mouse model of prostate cancer

Downregulation of Innate and Acquired Antitumor Immunity by Bystander gamma delta and alpha beta T Lymphocytes with Th2 or Tr1 Cytokine Profiles

T Cell-Mediated, IFN-γ-Facilitated Rejection of Murine B16 Melanomas

Contact Info

Product

Resources

About