Requirement of a Thymus Dependent Immune Response for Bcg-mediated Antitumor Activity

Ratliff, Timothy L.; Gillen, Daniel; Catàlona, William J.

doi:10.1016/s0022-5347(17)43909-7

Cited by 207 publications

(93 citation statements)

References 6 publications

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“…The question is whether these changes speci®cally target tumour cells or whether the in¯ammatory response to BCG also kills tumour cells in a`bystander' effect. The action of BCG appears to be T cell-dependent, as con®rmed by the present observation of T cell in®ltration of the suburothelial lamina propria, and by other reports [20,21]. The present study con®rms that in®ltrating T cells are immunologically active (interleukin-2-receptor-positive) [20].…”

Section: Discussionsupporting

confidence: 90%

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette‐Guérin treatment

Saint¹,

Patard²,

Muscatelli³

et al. 2001

BJU International

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Objective To compare the immunological status of normal and peritumoral bladder walls, and to characterize immunocompetent cells before and during intravesical instillations of bacillus Calmette-Gue Ârin (BCG). Patients and methods Twenty-three patients with super®cial urothelial bladder carcinoma (stages pTa to pT1, grades 1±3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopically normal bladder wall were taken before, 3 weeks and 3 months after BCG instillation. The controls comprised bladder biopsy specimens from 13 brain-dead ventilated kidney donors. Local in®ltrating cell types, i.e. lymphocyte in®ltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, cd), macrophages and dendritic cells, adhesion and costimulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semiquantitative immunohistochemical analysis.Results Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, activated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunological variables was transient, with a return to baseline 3 months after BCG instillation. Conclusions These results support the concept that there is a host-immune escape associated with bladder cancer. BCG therapy may temporarily restore impaired tumour rejection mechanisms in the peritumoral bladder wall, suggesting a need for maintenance therapy after the ®rst course of BCG.

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Section: Discussionsupporting

confidence: 90%

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette‐Guérin treatment

Saint¹,

Patard²,

Muscatelli³

et al. 2001

BJU International

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“…Effective BCG therapy requires induction of a T-cell-mediated immune response (Ratliff et al, 1987;Ratliff, 1992) and the activation of a natural killer (NK) cell-like population with an apparent ability to distinguish between normal and cancer cells (Bohle et al, 1993;Brandau et al, 2001). Significantly, both T-celland NK-cell-deficient mice respond poorly to BCG therapy (Brandau et al, 2001).…”

mentioning

confidence: 99%

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

et al. 2003

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Intravesical bacillus Calmette -Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS-and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer.

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“…Congenital T lymphocyte-delicicnt mice transplanted with bladder tumours fail to respond to intravesica! BCG Ircattnent until T lymphocytes are given [6]; this result shows [hat successful intravesica! BCCJ immunotherapy depends on an intact cellular immune function.…”

Section: Introductionmentioning

confidence: 78%

Induction of tumour necrosis factor-alpha (TNF-α) mRNA in bladders and spleens of mice after intravesical administration of bacillus Calmette-Guérin

Shin

Park

Kim

et al. 1995

Clinical and Experimental Immunology

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SUMMARYIntravesical bacillus Calmette-Guerin (BCG) therapy is highly eflfective in the therapy of carcinoma in situ of the bladder, but the mechanism of BCG immunotherapy is not clearly understood. We studied the production of TNF-n in spleens and bladders ofmice after intravesical BCG or BCG/interferon-gamma (iFN--}) instillation. Significant change of TNF-a mRNA expression of spleens and bladders of C3H/He mice was observed after intravesical BCG instillation, although intravesical IFN-7 therapy 3 days after BCG instillation to maintain the activated state of monocyte/macrophage lineage cells did not show a significant change of TNF-a mRNA, compared with that of BCG therapy alone. Maximal production of TNF-a mRNA in spleens of mice was seen after the first or second intravesical BCG instillation, and production of TNF-fi mRNA in bladders was also increased after intravesical BCG instillation. The increment of TNF-rt production by BCG stimulation in HL-60. a promyelocytic leukaemic cell line, and peripheral blood mononuclear cells in vitro may support Ihe in vivo effect of BCG therapy on the bladder. These data show that local production of TNF-a as well as systemic production by intravesical BCG treatment may correlate with one of the mechanisms of BCG immunotherapy of superficial bladder cancer.

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Requirement of a Thymus Dependent Immune Response for Bcg-mediated Antitumor Activity

Cited by 207 publications

References 6 publications

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette‐Guérin treatment

Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette‐Guérin treatment

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

Induction of tumour necrosis factor-alpha (TNF-α) mRNA in bladders and spleens of mice after intravesical administration of bacillus Calmette-Guérin

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