Melanoma Cells Treated with GGTI and IFN-γ Allow Murine Vaccination and Enhance Cytotoxic Response against Human Melanoma Cells

Sarrabayrouse, Guillaume; Pich-Bavastro, Christine; Moriez, Raphaël; Armand-Labit, Virginie; Rochaix, Philippe; Favre, Gilles; Tilkin–Mariamé, Anne-Françoise

doi:10.1371/journal.pone.0009043

Cited by 17 publications

(23 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because immune cell activities are often responses to external stimulation by other cell types, cocultures of cancer cells and immune cells are frequently used to assay specific immune cell activities, including changes in cytokine production and release [196][197][198], anti-cancer cytotoxic activities [199][200][201], and immune cell maturation and differentiation [202,203]. Interestingly, the communication between cancer cells and immune cells appears to be bidirectional, with immune cells also modulating cancer cell characteristics such as migratory potentials [204,205] and chemokine production [206].…”

Section: Co-cultures With Immune Cellsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

156

134

View full text Add to dashboard Cite

The development of novel cancer therapeutics is often plagued by discrepancies between drug efficacies obtained in preclinical studies and outcomes of clinical trials. The inconsistencies can be attributed to a lack of clinical relevance of the cancer models used for drug testing. While commonly used in vitro culture systems are advantageous for addressing specific experimental questions, they are often gross, fidelity-lacking simplifications that largely ignore the heterogeneity of cancers as well as the complexity of the tumor microenvironment. Factors such as tumor architecture, interactions among cancer cells and between cancer and stromal cells, and an acidic tumor microenvironment are critical characteristics observed in patient-derived cancer xenograft models and in the clinic. By mimicking these crucial in vivo characteristics through use of 3D cultures, co-culture systems and acidic culture conditions, an in vitro cancer model/microenvironment that is more physiologically relevant may be engineered to produce results more readily applicable to the clinic.

show abstract

Section: Co-cultures With Immune Cellsmentioning

confidence: 99%

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Choi¹,

Lin²,

Gout³

et al. 2014

Advanced Drug Delivery Reviews

156

134

View full text Add to dashboard Cite

show abstract

“…We have previously shown that treatments of melanoma cells with mevalonate pathway pharmacological inhibitors, notably statins, and in combination with IFNγ favor the anti-tumor adaptive immune response by inducing MHC class I and costimulatory molecule (CD80/CD86) overexpression (Tilkin-Mariame et al, 2005; Sarrabayrouse et al, 2010). We then asked the question whether or not these inhibitors could also favor the anti-melanoma innate immune response.…”

Section: Introductionmentioning

confidence: 99%

Statins Reduce Melanoma Development and Metastasis through MICA Overexpression

Pich-Bavastro¹,

Teiti²,

Rochaix³

et al. 2013

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Survival of melanoma patients after metastases detection remains short. Several clinical trials have shown moderate efficiency in improving patient survival, and the search for pharmacological agents to enhance the immune response and reduce melanoma metastases is still necessary. Statins block the mevalonate pathway, which leads to decreases in GTPase isoprenylation and activity, particularly those of the Ras superfamily. They are widely used as hypocholesterolemic agents in cardiovascular diseases and several studies have shown that they also have protective effects against cancers. Furthermore, we have previously demonstrated that treatment of melanoma cells with inhibitors of the mevalonate pathway, such as statins, favor the development of specific adaptive immune responses against these tumors. In the present study, we tested statin impact on the innate immune response against human metastatic melanoma cells. Our data shows that treatment of two human melanoma cell lines with statins induced a weak but significant increase of MHC class I Chain-related protein A (MICA) membrane expression. Peroxisome Proliferator-Activated Receptor gamma is involved in this statin-induced MICA overexpression, which is independent of Ras and Rho GTPase signaling pathways. Interestingly, this MICA overexpression makes melanoma cells more sensitive to in vitro lysis by NK cells. The impact of statin treatment on in vivo development of melanoma tumors and metastases was investigated in nude mice, because murine NK cells, which express NKG2D receptors, are able to recognize and kill human tumor cells expressing MICA. The results demonstrated that both local tumor growth and pulmonary metastases were strongly inhibited in nude mice injected with statin-treated melanoma cells. These results suggest that statins could be effective in melanoma immunotherapy treatments.

show abstract

“…Moreover inhibition of RhoA/ROCK pathway is also induced by Atorvastatin treatment at 1 and 5 μM, indeed the statins block the mevalonate pathway leading to decrease isoprenylation of Ras and Rho GTPases, which blocks their activity. Our previous papers have shown that inhibition of RhoA/ROCK activity favors anti-melanoma immune response through MHC-class I, costimulatory molecules and FasL overexpression on melanoma cells membrane [3][4][5]. Furthermore, as previously described, the inhibition of ROCK activity reduces melanoma cells migration, invasion and metastases [23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 63%

“…Interestingly Collisson et al showed that, independently of the immune response, and at plasma concentrations similar to those used to treat hypercholesterolemia, atorvastatin inhibited the in vivo metastasis of melanoma cells overexpressing RhoC [17]. In our previous work we have shown that inhibitors of the RhoA GTPase favor an adaptive antimelanoma immune response [3][4][5], and more recently we have described a beneficial role of statins in favoring the innate component of this immune response [6]. The present paper reinforces the idea that statins, and in particular atorvastatin, could be promising drugs for melanoma therapy.…”

Section: Discussionmentioning

confidence: 93%

“…During the oncogenic process, tumor cells must overcome inherent but also micro environmental control mechanisms, among which the innate and adaptive immune responses play a major role [2]. Interestingly, some pharmacological drugs such as statins render melanoma cells more immunogenic for the both the innate and adaptive anti-tumor immune responses [3][4][5]. We have previously shown that the in vitro treatment of human melanoma cells with atorvastatin or lovastatin enhanced tumor membrane expression of the MHC class I chain-related protein A (MICA), which is a ligand of the NKG2D activating receptor of NK cells [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Atorvastatin-Induced Inhibition of Human Melanoma In Vivo Development

Teiti¹,

Sarrabayrouse²

2016

Immunother Open Acc

View full text Add to dashboard Cite

Statins, 3-hydroxy 3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, are pleiotropic pharmacological inhibitors, which block the mevalonate synthesis pathway. They are widely used as hypocholesterolemic agents and have shown protective effects against cancers.Our previous data showed that statin treatment induced MHC class I chain-related protein A (MICA) membrane overexpression in human melanoma cells, which increased their sensitivity to NK cell cytotoxicity and thus the inhibition of tumor development. MICA is a ligand of the NK cell activating receptor NKG2D. This receptor is essential for NK cell control of tumor development and it has the unique property of being able to recognize tumor cells of both murine and human origin.Here, using atorvastatin and the WM-266-4 melanoma cell line, we first confirmed that statin treatment enhances MICA membrane expression and decreases local tumor growth and pulmonary metastasis implantation in vivo. Furthermore our new experiments showed that atorvastatin intraperitoneal repeated injections induced a reduction of tumor growth following subcutaneous implantation of untreated WM 266-4 cells into NMRI nude mice and favored the innate anti-melanoma immune response by increasing splenic NK cell concentration and activation. This report confirms that statins could become effective pharmacological agents for melanoma immunotherapy.

show abstract

Melanoma Cells Treated with GGTI and IFN-γ Allow Murine Vaccination and Enhance Cytotoxic Response against Human Melanoma Cells

Cited by 17 publications

References 22 publications

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Lessons from patient-derived xenografts for better in vitro modeling of human cancer

Statins Reduce Melanoma Development and Metastasis through MICA Overexpression

Atorvastatin-Induced Inhibition of Human Melanoma In Vivo Development

Contact Info

Product

Resources

About