Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients
Menée à partir d'échantillons tumoraux prélevés sur des patients atteints d'un mésothéliome et menée à l'aide d'un modèle murin, cette étude met en évidence les effets synergiques de la gemcitabine et des inhibiteurs de point de contrôle immunitaire contre les cellules cancéreuses, puis montre que cette combinaison thérapeutique peut lever la résistance tumorale à ces deux types d'agents
Purpose : Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment. Experimental Design : We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options. Results : The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy. Conclusions : Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.