Molecular characterization of defective antigen processing in human prostate cancer.

Molecular characterization of defective antigen processing in human prostate cancer. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Molecular characterization of defective antigen processing in human prostate cancer. Abstract Text:

BACKGROUND: Gene-modified tumor cell vaccines have shown efficacy in animal models of malignancy, including prostate cancer. Class I major histocompatibility complex (MHC) assembly and function in the cellular targets of such therapies is pivotal in determining the efficacy of specific cytokine-secreting tumor vaccines. PURPOSE: To help guide development of genetically engineered vaccine therapy for human prostate cancer, potential immune resistance pathways were evaluated by analysis of class I MHC assembly in prostate cancer cells. METHOD: Class I MHC assembly in metastasis-derived human prostate cancer cell lines (LNCaP, PPC-1, DU-145, PC-3, and TSU) and a normal prostate-derived cell line (TP-2) were characterized by phenotypic, molecular, and functional assays. Assembled class I MHC and antigen was measured by flow cytometry; mRNA levels of assembly components (class I MHC heavy chain, beta 2-microglobulin, and the antigen transporter gene product TAP-2) were determined; and antigen processing was measured with a chimeric reconstituted system using vaccinia vectors. Restoration of antigen processing was attempted by interferon gamma stimulation and by transfection with mouse class I MHC heavy-chain cDNA. RESULTS: Assembled class I MHC was underexpressed in two (LNCaP and PPC-1) of five prostate cancer cell lines compared with normal prostate-derived controls. PPC-1 cells underexpressed TAP-2 mRNA despite abundant class I MHC and beta 2-microglobulin message. Induction of TAP-2 by interferon gamma indicated that coding sequences for TAP-2 message were present in PPC-1. Resistance to cytotoxic T lymphocytes (CTL) lysis showed a functional defect in antigen transport by PPC-1 cells; reversal of the molecular defect with interferon gamma led to restoration of functional antigen processing. In contrast, LNCaP cells had competent antigen transport but deficient class I MHC heavy-chain function despite abundant class I MHC RNA; though refractory to stimulation by interferon gamma, this defect responded to transfection of class I MHC heavy-chain cDNA. CONCLUSIONS: Metastatic prostate cancer cells can escape T-cell recognition via divergent mechanisms of defective class I MHC assembly. The specific underexpression of TAP-2 gene product in PPC-1 cells contrasts with prior studies of TAP gene underexpression in lung cancer (which concurrently underexpressed class I MHC heavy chain) and provides evidence for a regulatory pathway controlling TAP-2 gene expression in human cancers that may not affect class I MHC heavy-chain expression. IMPLICATIONS: In clinical application of gene therapy for prostate cancer, these findings provide a rationale for focusing on strategies that can circumvent sole reliance on class I MHC-mediated tumor cell recognition by CTL.

Molecular characterization of defective antigen processing in human prostate cancer. Publishing Authors By Initials

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

PUBMED ID PMID:

MEDLINE DATE:

Molecular characterization of defective antigen processing in human prostate cancer. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the National Cancer Institute

VOLUME: 87

Page Numbers: 280-5

Journal Abbreviation: J. Natl. Cancer Inst.

ISSN: 0027-8874

DAY: 15

MONTH: Feb

YEAR: 1995

Molecular characterization of defective antigen processing in human prostate cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503089

Molecular characterization of defective antigen processing in human prostate cancer. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: therapy

Chemical & Substance for Abstract: Molecular characterization of defective antigen processing in human prostate cancer. Information

Substance Name: Histocompatibility Antigens Class I

Registry Number: 0

Grant and Affiliation Information for Molecular characterization of defective antigen processing in human prostate cancer.

AFFILIATION: Brady Urological Institute and Oncology Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Country: UNITED STATES

AGENCY: United States NCI

GRANT: Z01 BC010763-01

ACRONYM: BC

MEDLINETA: J Natl Cancer Inst

REFSOURCE: J Natl Cancer Inst. 1995 Feb 15;87(4):24

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Molecular characterization of defective antigen processing in human prostate cancer Related Publications

• (1)H NMR spectral simplification with achiral and chiral lanthanide shift reagents - IV. Thiopental and barbiturate analogues.
• 333.
• Active internal re-warming using a centrifugal pump and heat exchanger following haemorrhagic shock, surgical trauma and hypothermia in a porcine model.
• Adaptation of trigeminal ganglion cells to periodic whisker deflections.
• Affective differences among daily tobacco users, occasional users, and non-users.
• Angularly nonspecific response suppression in rat barrel cortex.
• Antiangiogenic plasma activity in patients with systemic sclerosis.
• Attending to affect: appraisal strategies modulate the electrocortical response to arousing pictures.
• Buprenorphine and methadone: a comparison of patient completion rates during inpatient detoxification.
• Designing medication safety in the NICU.
• Detergent resistance as a tool in membrane research.
• Discovery of the smallest Fayum Egyptian primates (Anchomomyini, Adapidae).
• Hypoxia-inducible factor-1 in human breast and prostate cancer.
• Inference in regression models of heavily skewed alcohol use data: A comparison of ordinary least squares, generalized linear models, and bootstrap resampling.
• It's worse than you thought: the feedback negativity and violations of reward prediction in gambling tasks.
• Kinetics of cell division in epidermal maintenance.
• Layer- and cell-type-specific effects of neonatal whisker-trimming in adult rat barrel cortex.
• Molecular characterization of defective antigen processing in human prostate cancer.
• Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice.
• Nanotechnology applications in cancer.
• Patency of endovascular treatment for central venous stenosis: is there a difference between dialysis fistulas and grafts?
• Percutaneous sodium tetradecyl sulfate sclerotherapy for peripheral venous vascular malformations: a single-center experience.
• Private lives and public programs: an Australian longitudinal study of the elderly.
• Prospective teratology of Retinoic Acid Metabolic Blocking Agents (RAMBAs) and loss of CYP26 activity.
• Pubertal maturation and early substance use risks among African American children.
• Resolution of a heart abnormality? - basketball: 1126: june 1 4:15 PM - 4:35 PM.
• Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils.
• Silky, sticky chimeras-designer VEGFs display their wares.
• The extracellular matrix and blood vessel formation: not just a scaffold.
• Wearable Wireless Telemetry System for Implantable Bio-MEMS Sensors.