Checkpoint modulation – A new way to direct the immune system against renal cell carcinoma

Immune checkpoint modulation in renal cell carcinoma

In this paper, Bedke and colleague highlight the way that patients treated for the metastatic disease in renal cell carcinoma (mRCC) by a cytokine treatment (cytokine Il-2 and IFN-α alone or combine with 5-Fluoracil) have experienced a disease stabilization or remission in up of 30% of the patients. But only for some months. It is a limited therapy due to the increase of regulatory T cells (Tregs and decreasing of circulating myeloid and plasmacytoid dendritic cells. In this paper, the authors highlight a new way to address renal cell carcinoma treatment targetting immune checkpoint modulation (PD-1, CTLA-4,…). They review the ongoing clinical data linked to the use of such immune checkpoint modulation pathway in the renal carcinoma.

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Summary | The introduction of targeted therapies like the tyrosine kinase (TKI) and mammalian target of rapamycin (mTOR) inhibitors has improved patients survival in general. Nevertheless, the prognosis remains limited. Therapies with a new mode of action are urgently warranted, especially those who would provoke long-term responders or long-lasting complete remissions as observed with unspecific immunotherapy with the cytokines interleukin-2 and interferon-a. In the recent years, a deeper understanding of the underlying immunology of T cell activation led to the development of checkpoint inhibitors, which are mainly monoclonal antibodies and which enhances the presence of the co-stimulatory signals needed for T cell activation or priming. This review discusses the clinical data and ongoing studies available for the inhibition of the PD-1 (CD279) and CTLA-4 (CD152) axis in mRCC. In addition, potential future immunological targets are discussed. This approach of T-cell activation or re-activation by immunological checkpoint inhibition holds the inherent promise to directly affect the tumor cell and thereby to potentially cure a subset of patients with mRCC.

LEARN MORE | Bedke et al. Hum. Vaccines Immunother, 2015

Check point modulators_Metastatic renal cell carcinoma_Cherry Biotech Metastatic renal cell carcinoma

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