Fas ligand and TNF-related apoptosis-inducing ligand induction on infiltrating lymphocytes in bladder carcinoma by bacillus Calmette-Guérin treatment.
OBJECTIVE
To determine the molecular mechanisms underlying the efficacy of bacillus Calmette-Guérin (BCG) therapy against superficial carcinoma of the urinary bladder, we evaluated the expression of cytotoxic molecules on tumor-infiltrating lymphocytes before and after therapy.


METHODS
Immunofluorescence staining allowed the specific detection of Fas, Fas ligand (FasL), and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression on tumor cells and the respective leukocyte populations in biopsy samples from 6 patients.


RESULTS
Significant increases in the infiltration of FasL- and TRAIL-expressing CD4+ T cells and macrophages and FasL-expressing CD8+ T and NK cells were observed after BCG instillation in bladder carcinoma. Moreover, Fas expression was upregulated on tumor cells after BCG instillation.


CONCLUSIONS
The data suggested that the enhanced infiltration of FasL- and/or TRAIL-expressing leukocytes (CD4+ T cells, CD8+ T cells, natural killer cells and macrophages) and the induction of Fas expression on tumor cells may play an important role in the therapeutic effect of BCG instillation.
Mehmut
Murat
M
Department of Urology, Juntendo University School of Medicine, Tokyo, Japan.
Takeda
Kazuyoshi
K
Abe
Masaaki
M
Ogata
Hideko
H
Hirose
Sachiko
S
Okumura
Ko
K
Fujime
Makoto
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000283:Administration, Intravesical; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007958:Leukocyte Count; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D012189:Retrospective Studies; D053221:TNF-Related Apoptosis-Inducing Ligand; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D000276:Adjuvants, Immunologic; D051017:Apoptosis Regulatory Proteins; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha