Interleukin-10 inhibits<i>Mycobacterium bovis</i>bacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells

Luo, Yi; Han, Rong; Evanoff, David P.; Chen, X

doi:10.1111/j.1365-2249.2010.04105.x

Cited by 58 publications

(69 citation statements)

References 55 publications

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“…We have also demonstrated that blocking IL-10 signal transduction by anti-IL-10R1 mAb that binds to IL-10R1 enhances BCG-induced anti-bladder cancer immunity in a similar mouse model of bladder cancer (Bockholt et al, 2012). In addition to in vivo studies, we have observed the inhibitory effect of IL-10 on BCG induced macrophage cytotoxicity against bladder cancer cells in vitro through antibody neutralization of IL-10 for wild-type macrophage cultures or use of IL-10 -/-macrophages in assays (Luo et al, 2010).…”

Section: Il-10 In Bcg Treatment Of Bladder Cancermentioning

confidence: 82%

Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

P.¹

2012

American Journal of Immunology

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Problem statement: Bladder cancer is a common urologic cancer and intravesical Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the mainstay in the treatment of superficial bladder cancer. However, the current BCG therapy is not desirable with respect to its efficacy and side effects. Interleukin (IL)-10, a T helper type (Th) 2 cytokine, plays an important regulatory role in bladder cancer immunosurveillance and BCG immunotherapy. Therefore, blocking IL-10 activity could be beneficial for bladder cancer patients undergoing BCG therapy. Approach: Treatment with intravesical BCG in combination with systemic IL-10 monoclonal antibody (mAb) specific for IL-10 neutralization or IL-10 receptor (IL-10R) blockage has been evaluated in preclinical bladder cancer models. Results: Addition of anti-IL-10 neutralizing mAb or anti-IL-10R1 mAb enhances BCG induction of Th1 immune responses and anti-bladder cancer immunity. Conclusion/Recommendations: BCG immunotherapy of bladder cancer can be enhanced by addition of IL-10 blocking mAb. Future studies should aim to explore the mechanisms underlying the induction of enhanced antitumor immunity by BCG combination therapy and develop therapeutic regimens for clinical evaluation of the safety and efficacy of BCG combination therapy.

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Section: Il-10 In Bcg Treatment Of Bladder Cancermentioning

confidence: 82%

Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

P.¹

2012

American Journal of Immunology

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“…Th2 lymphocytes release cytokines such as IL-4, IL-6, IL-10, IL-13, IL-18 that promote humoral immune responses, [25]. Between Th1 and Th2 lymphocytes, phenomenon of mutual suppression activity is observed.…”

Section: Discussionmentioning

confidence: 99%

Effect of Different Bacillus Calmette-Guerin Substrains on Growth Inhibition of T24 Bladder Cancer Cells and Cytokines Secretion by BCG Activated Peripheral Blood Mononuclear Cells of PBMCs

Janaszek-Seydlitz¹,

Prygiel²,

Bucholc³

et al. 2014

Adv Clin Exp Med

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Background. Bladder carcinoma is the most common malignancy of the urinary tract. Approximately 75-85% of patients present non-muscle invasive bladder cancer (NMIBC). Standard primary treatment for NIMBC is transurethral resection (TUR) followed by intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. BCG has been accepted as the most effective agent in clinical use against NMIBC. Various BCG substrains are used worldwide for bladder cancer immunotherapy although the impact of used BCG substrain on BCG antitumor capacity is a little investigated. Objectives. The aim of this study was to compare the antitumor capacity and the ability to trigger cytokines production of three BCG substrains by stimulation of the local innate immunity in vitro. Material and Methods. The human bladder cancer cell line T24 was co-cultured with each of the BCG substrains: Moreau, Tice and RIVM alone or with BCG pretreated DCs (dendric cells) and allogenic PBMCs derived from the same donor. The inhibition of T24 cell growth was evaluated by 3 H-thymidine incorporation. Production of Th1 cytokines (IFN-γ, TNF-α, IL-12) and Th2 cytokines (IL-10, IL-4) was measured in cultures of BCG-activated PBMCs by ELISA test.Results. An approximately two-fold inhibition of T24 cell proliferation was observed as a direct cytotoxic effect of tested BCG substrains on T24 cells. However, BCG inhibited the growth of tumor cells mainly by activating the effector cells of innate immunity. About a 10-fold inhibition of T24 cell proliferation was observed when T24 cells were co-cultured with allogenic BCG pretreated DC s and PBMCs derived from the same donor. The PBMCs activated by compared live BCG substrains secreted large amounts of TNF-α and IFN-γ cytokines. Conclusions. Tested BCG substrains had little direct inhibitory effect on T24 cell proliferation. Moreau evolutionarily early BCG substrain showed similar strong, indirect antitumor effects as evolutionarily late BCG substrains Tice and RIVM (Adv Clin Exp Med 2014, 23, 6, 877-884).

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“…[9,10] The cascade of events results in secretion of an array of cytokines, chemokines, and cytotoxicity mediators that can be detected in tissue and in urine. [7,11] These are summarized in Table 1. Examples are (1) pro-inflammatory, T helper type 1 (Th1) cytokines such as interleukin (IL)-1β, IL-2, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ; (2) Th2 cytokines IL-4 and IL-10; (3) chemokines, as CCL2, CCL8, CCL3, IFN-γ-inducible protein (IP-10), CXCL9; (4) cytotoxicity mediators, such as nitric oxide (NO) released by macrophages, and mediators of cytotoxic response such as perforin (Perf), granulysin (GNLY), and Fas ligand (Fas-L) pathway released by cytolytic lymphocytes [natural killer (NK) and T cytotoxic cells], and cytotoxic T lymphocyte antigen-4 (CTLA4) expressed by activated/exhausted T cell; and (5) molecules involved in stress homeostatic events such as heme oxygenase 1 (HMOX-1).…”

Section: Introductionmentioning

confidence: 99%

Systemic humoral responses of non-muscle-invasive bladder cancer during BCG treatment: less is more

Silva¹,

Videira²,

Ligeiro³

et al. 2017

JCMT

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Interleukin-10 inhibitsMycobacterium bovisbacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells

Cited by 58 publications

References 55 publications

Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

Role of IL-10 in Urinary Bladder Carcinoma and Bacillus Calmette-Guerin Immunotherapy

Effect of Different Bacillus Calmette-Guerin Substrains on Growth Inhibition of T24 Bladder Cancer Cells and Cytokines Secretion by BCG Activated Peripheral Blood Mononuclear Cells of PBMCs

Systemic humoral responses of non-muscle-invasive bladder cancer during BCG treatment: less is more

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