NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation

García‐Cuesta, Eva M.; López‐Cobo, Sheila; Maestro, M. Álvarez; Esteso, Gloria; Romera-Cárdenas, Gema; Rey, M.; Cassady-Cain, Robin L.; Linares, Ana María; Valés-Gómez, Alejandro; Reyburn, Hugh; Martínez‐Piñeiro, Luis; Valés‐Gómez, Mar

doi:10.3389/fimmu.2015.00284

Cited by 30 publications

(36 citation statements)

References 41 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NK cells may contribute to the non-specific (heterologous) benefits of BCG vaccination [30]. The cells are activated by BCG vaccine non-specifically after re-stimulation as evidenced by increasing expressing IL-2 in mice immunized with BCG vaccine but not after mock immunization [50]. Likewise, peripheral CD4 + T cells produced more IFN-γ and TNF-α after BCG vaccination and these two cytokines are important in control of M.tb infection[51,52].…”

Section: Discussionmentioning

confidence: 99%

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination

Chen¹,

Yan²,

et al. 2017

Journal of Controlled Release

View full text Add to dashboard Cite

Live attenuated Bacille Calmette-Guerin (BCG) bacillusis the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradeemally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, the individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise.While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin.

show abstract

Section: Discussionmentioning

confidence: 99%

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination

Chen¹,

Yan²,

et al. 2017

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…In a mouse model, depletion of NK cells also reduced efficacy of BCG immunotherapy . The role of NK cells in BCG‐induced cytotoxicity is supported by additional reports . However, in some in vitro and in vivo BCG studies, bladder cancer cell cytolysis or treatment efficacy in mice were not significantly affected by modulating NK cell activity .…”

Section: Mechanisms Of the Response Of Nmibc To Bcg Immunotherapymentioning

confidence: 73%

Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

Song

Powles

Shi

et al. 2019

The Journal of Pathology

View full text Add to dashboard Cite

With the mechanistic understanding of immune checkpoints and success in checkpoint blockade using antibodies for the treatment of certain cancers, immunotherapy has become one of the hottest areas in cancer research, with promise of long‐lasting therapeutic effect. Currently, however, only a proportion of cancers have a good response to checkpoint inhibition immunotherapy. Better understanding of the cancer response and resistance mechanisms is essential to fully explore the potential of immunotherapy to cure the majority of cancers. Bladder cancer, one of the most common and aggressive malignant diseases, has been successfully treated both at early and advanced stages by different immunotherapeutic approaches, bacillus Calmette–Guérin (BCG) intravesical instillation and anti‐PD‐1/PD‐L1 immune checkpoint blockade, respectively. Therefore, it provides a good model to investigate cancer immune response mechanisms and to improve the efficiency of immunotherapy. Here, we review bladder cancer immunotherapy with equal weight on BCG and anti‐PD‐1/PD‐L1 therapies and demonstrate why and how bladder cancer can be used as a model to study the predictors and mechanisms of cancer immune response and shine light on further development of immunotherapy approaches and response predictive biomarkers to improve immunotherapy of bladder cancer and other malignancies. We review the success of BCG and anti‐PD‐1/PD‐L1 treatment of bladder cancer, the underlying mechanisms and the therapeutic response predictors, including the limits to our knowledge. We then highlight briefly the adaptation of immunotherapy approaches and predictors developed in other cancers for bladder cancer therapy. Finally, we explore the potential of using bladder cancer as a model to investigate cancer immune response mechanisms and new therapeutic approaches, which may be translated into immunotherapy of other human cancers. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

show abstract

“…Additionally, IL-2 may promote the proliferation and cytotoxicity of NK cells (29). In H22-bearing mice, the secretion of IFN-γ, TNF-α and IL-2 was elevated following Mel-P15 administration, suggesting that Mel-P15 increased the secretion of IL-2 and IFN-γ in tumor-bearing mice, thereby activating and maintaining the cytotoxicity of NK cells and eliminating H22 cells.…”

Section: Discussionmentioning

confidence: 99%

The anti‑hepatocellular carcinoma activity of Mel‑P15 is mediated by natural killer cells

Cui

Peng

et al. 2017

Oncol Lett

View full text Add to dashboard Cite

Abstract. Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 µg/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61.15% following treatment with 2 mg/kg Mel-P15. In addition, the immune response was activated following Mel-P15 treatment. Mel-P15 treatment increased the spleen and thymus indices, promoted splenocyte proliferation, stimulated NK cytotoxicity and upregulated the secretion of cytokines, including interleukin-2, interferon-γ and tumor necrosis factor-α. In addition, the tumor inhibitory effect of Mel-P15 on BEL-7402-bearing nude mice was abrogated by the selective depletion of NK cells via the intraperitoneal injection of an anti-asialo GM-1 antibody. The results suggest that Mel-P15 inhibits tumor growth in vivo by promoting NK cell cytotoxicity. Mel-P15 may therefore be a potential immunotherapy candidate for the treatment of hepatocellular carcinoma.

show abstract

NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation

Cited by 30 publications

References 41 publications

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination

Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

The anti‑hepatocellular carcinoma activity of Mel‑P15 is mediated by natural killer cells

Contact Info

Product

Resources

About