Immunothérapie des cancers du rein

Abstract

Clear cell kidney cancer is a tumour type whose development and progression is driven by the HIF/VEGF angiogenesis pathway. Anti-angiogenic (AA) agents, particularly anti-VEGFR tyrosine kinase (TKI) inhibitors, have profoundly modified the prognosis of patients in the metastatic setting (mRCC) since their registration in 2006. At the same time, mTOR inhibitors have also brought significant benefit to patients. More recently, treatments restoring adaptive anti-tumor immunity, anti-program death 1 (anti-PD-1) checkpoint inhibitors (ICP), have in turn revolutionized the management of patients with mRCC. The multi-tumor efficacy of these ICPs proves the crucial role of anti-tumor immunity in tumor development and progression in a number of tumors including clear cell kidney tumours (ccRCC). The tumor immune microenvironment (TME) of ccRCC is known to be highly immunosuppressive. Thus ccRCCs are characterized by a strong infiltration of CD8+ T lymphocytes, frequently expressing immunological checkpoint molecules on their surface, giving them a poor prognostic feature. These characteristics partly explain the effectiveness of ICP in ccRCC and constitute a strong rationale for their further development, either at an earlier stage or in combination, particularly with AA or TKI. In this review are compiled the main clinical results of immunological checkpoint molecules alone or in combination in 1stline or after TKI failure.