Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence?

Finet, A.; Amini‐Adlé, Mona; Balme, B.; Colson, François; Thomas, Luc

doi:10.1007/s10067-012-2114-1

Cited by 14 publications

(10 citation statements)

References 23 publications

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“…[16] Rapid development of melanoma has been recently reported in two patients treated with an anti-IL-6 agent, tocilizumab. [1718] In our study, patients treated with biologic agents did not have more nevi than patients treated otherwise. It may be the result of low sample size of biologic agents in our study.…”

Section: Discussionmentioning

confidence: 49%

The relationship of psoriasis and melanocytic nevi

et al. 2016

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Background:There is limited data about the relationship between psoriasis and melanocytic lesions and melanoma. Immunologic pathways which were implicated in psoriasis induce a reduction in the number of melanocytic nevi.Aims and Objectives:To investigate the number of melanocytic nevi in psoriatic patients compared with controls and its relationship with disease severity and type of treatment.Methods:We performed a prospective study in 100 psoriatic patients and 100 controls. Clinical data were recorded for all participants.Results:As compared with controls, patients had overall fewer nevi congenital nevi. Among psoriatic patients, biologic agents and disease severity did not correlate with the number of nevi.Conclusions:Psoriatic patients have fewer nevi than controls. Frequency of nevi in psoriatic patients is not related to treatment and disease severity.

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Section: Discussionmentioning

confidence: 49%

The relationship of psoriasis and melanocytic nevi

et al. 2016

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“…2 ). This observation might be of clinical relevance as case reports have been published that tocilizumab, when administered to patients with rheumatoid arthritis, led to a rapid progression of early melanoma in two cases 46 , 47 . It is worth mentioning that, similar to melanoma, IL-6 plays a dualistic role in stage-dependent growth regulation of breast cancer 27 .…”

Section: Discussionmentioning

confidence: 72%

Tocilizumab unmasks a stage-dependent interleukin-6 component in statin-induced apoptosis of metastatic melanoma cells

et al. 2015

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The interleukin (IL)-6 inhibits the growth of early-stage melanoma cells, but not metastatic cells. Metastatic melanoma cells are susceptible to statin-induced apoptosis, but this is not clear for early-stage melanoma cells. This study aimed to investigate the IL-6 susceptibility of melanoma cells from different stages in the presence of simvastatin to overcome loss of growth arrest. ELISA was used to detect secreted IL-6 in human melanoma cells. The effects of IL-6 were measured by western blots for STAT3 and Bcl-2 family proteins. Apoptosis and proliferation were measured by caspase 3 activity, Annexin V staining, cell cycle analysis, and a wound-healing assay. Human metastatic melanoma cells A375 and 518A2 secrete high amounts of IL-6, in contrast to early-stage WM35 cells. Canonical IL-6 signaling is intact in these cells, documented by transient phosphorylation of STAT3. Although WM35 cells are highly resistant to simvastatin-induced apoptosis, coadministration with IL-6 enhanced the susceptibility to undergo apoptosis. This proapoptotic effect of IL-6 might be explained by a downregulation of Bcl-XL, observed only in WM35 cells. Furthermore, the IL-6 receptor blocking antibody tocilizumab was coadministered and unmasked an IL-6-sensitive proportion in the simvastatin-induced caspase 3 activity of metastatic melanoma cells. These results confirm that simvastatin facilitates apoptosis in combination with IL-6. Although endogenous IL-6 secretion is sufficient in metastatic melanoma cells, exogenously added IL-6 is needed for WM35 cells. This effect may explain the failure of simvastatin to reduce melanoma incidence in clinical trials and meta-analyses.

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“…Differentiated melanoma cells were thus more responsive to immune recognition by T cells specific for lineage‐related antigens, likely elicited by the allogeneic vaccine. Moreover, two distinct and independent case reports described that patients undergoing prolonged treatment with the IL‐6Rα blocking antibody tocilizumab developed very aggressive malignant melanoma . The prolonged absence of IL‐6‐mediated signaling might have supported the expansion of tumor bulk enriched in TICs, displaying a low frequency of differentiated melanoma cells and thus likely evading immunosurveillance.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells

et al. 2016

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Melanoma is a highly heterogeneous tumor for which recent evidence supports a model of dynamic stemness. Melanoma cells might temporally acquire tumor-initiating properties or switch from a status of tumor-initiating cells (TICs) to a more differentiated one depending on the tumor context. However, factors driving these functional changes are still unknown. We focused on the role of cyto/chemokines in shaping TICs isolated directly from tumor specimens of two melanoma patients, namely Me14346S and Me15888S. We analyzed the secretion profile of TICs and of their corresponding melanoma differentiated cells and we tested the ability of cyto/chemokines to influence TIC self-renewal and differentiation. We found that TICs, grown in vitro as melanospheres, had a complex secretory profile as compared to their differentiated counterparts. Some factors, such as CCL-2 and IL-8, also produced by adherent melanoma cells and melanocytes did not influence TIC properties. Conversely, IL-6, released by differentiated cells, reduced TIC self-renewal and induced TIC differentiation while IL-10, produced by Me15888S, strongly promoted TIC self-renewal through paracrine/autocrine actions. Complete neutralization of IL-10 activity by gene silencing and antibody-mediated blocking of the IL-10Rα was required to sensitize Me15888S to IL-6-induced differentiation. For the first time these results show that functional heterogeneity of melanoma could be directly influenced by inflammatory and suppressive soluble factors, with IL-6 favoring TIC differentiation, and IL-10 supporting TIC self-renewal. Thus, understanding the tumor microenvironment (TME) role in modulating melanoma TIC phenotype is fundamental to identifying novel therapeutic targets to achieve long-lasting regression of metastatic melanoma. Stem Cells 2016;34:2449-2460.

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Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cause or coincidence?

Cited by 14 publications

References 23 publications

The relationship of psoriasis and melanocytic nevi

The relationship of psoriasis and melanocytic nevi

Tocilizumab unmasks a stage-dependent interleukin-6 component in statin-induced apoptosis of metastatic melanoma cells

Immunomodulatory Factors Control the Fate of Melanoma Tumor Initiating Cells

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