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Anticancer effect of imatinib via immunostimulation

the Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, IGR, Villejuif, France
Nature medicine (Impact Factor: 28.05). 09/2011; 17(9):1050-1. DOI: 10.1038/nm.2429
Source: PubMed
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    • "In addition to selectively inhibit the tumor cells, imatinib was found to be able to induce indirect effects on immune system by stimulating autoimmune response. Therefore, it is tempting to speculate that the action of imatinib in PVNS could be also related to this indirect effect, already reported for gastrointestinal stromal tumor (GIST) patients [10,11]. In diffuse-type PVNS this effect could be even more relevant given the significant amount of inflammatory component detectable in this disease. "
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    ABSTRACT: Background Pigmented villonodular synovitis (PVNS) is a rare locally aggressive tumor. PVNS is characterized in most cases by a specific t(1;2) translocation, which fuses the colony stimulating factor-1 (CSF1) gene to the collagen type VIa3 (COL6A3) promoter thus leading through a paracrine effect to the attraction of non-neoplastic inflammatory cells expressing CSF1-receptor. Imatinib is a tirosin-kinase inhibitors (TKI) active against CSF1-receptor whose activity in naïve PVNS was already described. We report on two PVNS patients who responded to imatinib after failure to nilotinib, another CSF1-receptor inhibitor. Methods Since August 2012, 2 patients with progressive, locally advanced PVNS resistant to nilotinib (Patient 1: man, 34 years; Patient 2: woman, 24 years) have been treated with second-line imatinib 400 mg/day. Both patients are evaluable for response. Results Both patients are still on treatment (7 and 4 months). Patient 1 had a dimensional response by MRI after 2 months from starting imatinib, together with symptomatic improvement. In Patient 2 a metabolic response was detected by [18F]fluorodeoxyglucose–positron emission tomography (PET) at 6 weeks coupled with tumor shrinkage by MRI, and symptomatic improvement. Conclusions Imatinib showed antitumor activity in 2 patients with nilotinib-resistant PVNS. This observation strengthen the idea that targeted agent with similar profile can give a different clinical result, as already described for gastrointestinal stromal tumor (GIST) patients treated with the same agents. Molecular studies are needed to clarify the biologic mechanism(s) underlying the response.
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