Immunotherapy Resistance Mechanisms in Renal Cell Cancer
Katarzyna Kaminska, Gabriel Wcislo, Anna M. Czarnecka, Salem Chouaib and Cezary Szczylik
Affiliation: Laboratory of Molecular Oncology, Military Institute of Medicine, Warsaw, Szaserow 128, 04-141 Warsaw, Poland.
Keywords: Renal cell carcinoma, immunotherapy resistance, renal cell cancer chemotherapy, renal cell cancer radiotherapy,
IL-2 induced immunotherapy, IFN induced immunotherapy, TKI induced immunotherapy.
The successful treatment of renal cancer remains a therapeutic challenge. Clear Cell Renal Cell Carcinoma
(ccRCC) is resistant to conventional radio and chemotherapy, but complete response has been observed after
immunotherapy with high-dose interleukin-2 (IL-2) and interferon (IFN)-α. Nevertheless, immunotherapy strategies
have shown response rates in the range of 5 to 10%. For the past 20 years, the mechanisms of treatment resistance have
been studied, and immune escape of tumours in cancer development and spread has been a broadly investigated
phenomenon. Multiple studies have revealed that genomic abnormalities of ccRCC promote the loss of major
histocompatibility complex (MHC) molecules on the renal cancer cell surface, resulting in immune response resistance.
Studies have shown that IFN-α-induced signalling pathways are deregulated in ccRCC cells and promote immune escape.
Polymorphisms of multiple genes, including STAT3, have been shown to trigger immune-response deregulation.
Investigation and understanding of the mechanisms of renal cell cancer immunotherapy resistance are extremely important
for the design of rational combinatorial approaches and other novel therapies in the future. This mini-review focuses on
immunotherapy resistance mechanisms in ccRCC.
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