EurekaMag
+ Most Popular
Cunninghamia lanceolata plantations in China
Mammalian lairs in paleo ecological studies and palynology
Studies on technological possibilities in utilization of anhydrous milk fat for production of recombined butter-like products
Should right-sided fibroelastomas be operated upon?
Large esophageal lipoma
Apoptosis in the mammalian thymus during normal histogenesis and under various in vitro and in vivo experimental conditions
Poissons characoides nouveaux ou non signales de l'Ilha do Bananal, Bresil
Desensitizing efficacy of Colgate Sensitive Maximum Strength and Fresh Mint Sensodyne dentifrices
Administration of fluid by subcutaneous infusion: revival of a forgotten method
Tundra mosquito control - an impossible dream?
Schizophrenia for primary care providers: how to contribute to the care of a vulnerable patient population
Geochemical pattern analysis; method of describing the Southeastern limestone regional aquifer system
Incidence of low birth weights in a hospital of Mexico City
Tabanidae
Graded management intensity of grassland systems for enhancing floristic diversity
Microbiology and biochemistry of cheese and fermented milk
The ember tetra: a new pygmy characid tetra from the Rio das Mortes, Brazil, Hyphessobrycon amandae sp. n. (Pisces, Characoidei)
Risk factors of contrast-induced nephropathy in patients after coronary artery intervention
Renovation of onsite domestic wastewater in a poorly drained soil
Observations of the propagation velocity and formation mechanism of burst fractures caused by gunshot
Systolic blood pressure in a population of infants in the first year of life: the Brompton study
Haematological studies in rats fed with metanil yellow
Studies on pasteurellosis. I. A new species of Pasteurella encountered in chronic fowl cholera
Dormancy breaking and germination of Acacia salicina Lindl. seeds
therapy of lupus nephritis. a two-year prospective study

Role of Fas and granule exocytosis pathways in tumor-infiltrating T lymphocyte-induced apoptosis of autologous human lung-carcinoma cells


Role of Fas and granule exocytosis pathways in tumor-infiltrating T lymphocyte-induced apoptosis of autologous human lung-carcinoma cells



International Journal of Cancer 91(6): 772-777



ISSN/ISBN: 0020-7136

PMID: 11275978

DOI: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1132>3.0.co;2-v

We have isolated a cytotoxic T lymphocyte (CTL) clone, Heu161, that reacts specifically with the human autologous lung carcinoma cell line IGR-Heu. We first demonstrated that IGR-Heu lacked Fas-receptor expression and was resistant to CD95-induced apoptosis. To further elucidate the role of Fas in tumor immune surveillance, we have stably transfected IGR-Heu with a Fas-expression vector and isolated CD95-sensitive and -resistant clones. Our data indicated that the resistance of 2 selected Fas-transfected clones to CD95-mediated lysis correlated with down-regulation of caspase-8 or its lack of cleavage and subsequent activation. All Fas transfectants, either sensitive or resistant to anti-Fas agonistic antibody, were as efficiently lysed by the CTL clone as the parental cell line. In addition, neither anti-Fas-blocking antibody nor Fas-Fc molecule inhibited T-cell lysis of Fas-sensitive tumor clone. This cytotoxicity was extracellular Ca(2+)-dependent and abolished in the presence of EGTA, indicating that it was mainly granzyme-mediated. Interestingly, although the caspase inhibitor z-VAD-fmk had no effect on tumor-cell lysis, it efficiently blocked target DNA damage triggered by autologous CTLs via the granule exocytosis pathway, indicating that the latter event was caspase-dependent. The present results suggest that lung carcinoma-specific CTLs use mainly a granule exocytosis-dependent pathway to lyse autologous target cells and that these effectors are able to circumvent alteration of the Fas-triggered intracellular signalling pathway via activation of a caspase-independent cytoplasmic death mechanism.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011308527

Download citation: RISBibTeXText

Related references

Human accessory cells activate fresh, autologous normal renal T-lymphocytes but not tumor infiltrating T-lymphocytes to lyse autologous tumor cells in a primary cytotoxic T-lymphocyte assay in renal-cell carcinoma. Journal of Urology 163(4 Suppl ): 115, 2000

Human accessory cells activate fresh, normal, tumor-distant T lymphocytes but not tumor-infiltrating T lymphocytes to lyse autologous tumor cells in a primary cytotoxic T lymphocyte assay in renal cell carcinoma. European Urology 40(4): 427-433, 2001

Level of Sorcin expression influences chemoresistance and overall survival in patients with ovarian cancer. Zhong Nan da Xue Xue Bao. Yi Xue Ban 44(10): 1113-1119, 2019

Distribution of tumor-infiltrating dendritic cells in human non-small cell lung carcinoma in relation to apoptosis. Pathology International 54(5): 302-310, 2004

Tumor-Infiltrating Cd4+ T Lymphocytes Express Apo2 Ligand (Apo2L)/Trail upon Specific Stimulation with Autologous Lung Carcinoma Cells: Role of Ifn- on Apo2L/Trail Expression and -Mediated Cytotoxicity. The Journal of Immunology 169(2): 809-817, 2002

Tumor-infiltrating CD4+ T lymphocytes express APO2 ligand (APO2L)/TRAIL upon specific stimulation with autologous lung carcinoma cells: role of IFN-a on APO2L/TRAIL expression and -mediated cytotoxicity. Journal of Immunology 169(2): 9-17, 2002

Tumor-infiltrating CD4+ T lymphocytes express APO2 ligand (APO2L)/TRAIL upon specific stimulation with autologous lung carcinoma cells: role of IFN-alpha on APO2L/TRAIL expression and -mediated cytotoxicity. Journal of Immunology 169(2): 809-817, 2002

Autologous tumor cell cytotoxicity and cytokine biosynthesis in T cells infiltrating human lung cancers. Proceedings of the American Association for Cancer Research Annual Meeting 39: 85, 1998

Interleukin 2 induced propagation of human tumor infiltrating lymphocytes with cytotoxic activity restricted to fresh autologous tumor cells. Proceedings of the American Association for Cancer Research Annual Meeting 29: 378, 1988

Study of head and neck cancer treatment by administration of autologous cytotoxic lymphocyte induced by stimulation with tumor cell. Effect of adoptive immunotherapy by intra-arterial infusion of killer cells stimulated by autologous tumor in patients with maxillary carcinoma. Nippon Jibiinkoka Gakkai Kaiho 91(12): 2069-2078, 1988

Study of head and neck cancer treatment by administration of autologous cytotoxic lymphocyte induced by stimulation with tumor cell--effect of adoptive immunotherapy by intra-arterial infusion of killer cells stimulated by autologous tumor in patients with maxillary carcinoma. Nihon Jibiinkoka Gakkai Kaiho 91(12): 2069-2078, 1988

The role of ERK 1/2 and p38 MAP-kinase pathways in taxol-induced apoptosis in human ovarian carcinoma cells. Experimental Cell Research 268(1): 84-92, 2001

CD8(+) tumor-infiltrating T cells are deficient in perforin-mediated cytolytic activity due to defective microtubule-organizing center mobilization and lytic granule exocytosis. Journal of Immunology 167(9): 5042-5051, 2001

Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Research 47(1): 173-177, 1987

Enhancement of (-)-epigallocatechin-3-gallate and theaflavin-3-3'-digallate induced apoptosis by ascorbic acid in human lung adenocarcinoma SPC-A-1 cells and esophageal carcinoma Eca-109 cells via MAPK pathways. Biochemical and Biophysical Research Communications 438(2): 370-374, 2013