Immunotherapy Resistance Mechanisms in Renal Cell Cancer
Katarzyna Kaminska, Gabriel Wcislo, Anna M. Czarnecka, Salem Chouaib and Cezary Szczylik
The successful treatment of renal cancer is still a therapeutic challenge. Clear Cell Renal Cell Carcinoma (ccRCC) is resistant to conventional radio- and chemotherapy, but complete response have been observed after immunotherapy with high dose interleukin-2 (IL2) and interferon (IFN)-α. Nevertheless immunotherapy strategies showed overall low response rates in the range of 5% to 10%. The mechanisms of treatment resistance have been studied over last twenty years. Immune escape of tumors is a broadly investigated phenomenon in cancer development and spread. Multiple studies have revealed that genomic abnormalities of ccRCC promote the loss of MHC molecules on renal cancer cells surface resulting in immune response resistance. IFN-α induced signaling pathways have been found deregulated in ccRCC cells and described to promote immune escape. Finally polymorphisms of multiple genes, including STAT3, were described to trigger immune response deregulation. Investigation and understanding of the mechanisms of renal cell cancer immunotherapy resistance is extremely important in order to design rational combinatorial approaches and other novel therapies in the future. This mini-review focus on immunotherapy resistance mechanisms in ccRCC.
Department of Oncology with Laboratory of Molecular Oncology, Military Institute of Medicine, Warsaw, Poland.