Exploring immune therapy for renal cancer

Abstract

This implies thatclinically-detectable malignanciesderive from cancer cells previously“edited” by the host’s immunity. Itfollows that immunotherapy regi-mens must take into account the fact that the tumor hasalready found a way to circumvent immune recognition/elimination, including the creation of immune suppressivelocal tumor environments. It is therefore crucial to developstrategies aimed at overcoming such immunosuppressivemechanisms, as well as enhancing effector T cell responses.After many disappointments, years of effort in tumorimmunology have finally resulted in two important develop-ments in cancer immunotherapy. One is the US Food andDrugAdministration(FDA)approvalofsipuleucel-T,andtheother is the application of anti-cytotoxic T lymphocyteantigen4(CTLA-4)antibodytherapy.Thesetwoinnovations,together with the approval of tyrosine kinase inhibitors, willhave a huge impact on cancer immunotherapy for the treat-ment of renal cell carcinoma (RCC) and are likely to cause aparadigm shift in treatment rationales. The emphasis will beincreasingly on (i) overcoming immunosuppressive environ-ments rather than mere activation of immune responses; and(ii) a focus on the individual “patient response” rather than“tumor response”. I hope readers will get a sense of thisparadigmshiftincancerimmunotherapy.Inthiseditorial,wehave brought together a series of reviews from experts toexplore immune therapy for renal cancer.RCC, like malignant melanoma, appears to be one of themostimmune-sensitivecancersoccasionallyundergoingdra-matic spontaneous regressions. This has encouraged a strat-egy of using immunomodulating therapies more frequentlyfor these cancers than many others. Nearly two decades ago,cytokine-based therapy using high dose interleukin-2 (HDIL-2)wasapprovedbytheUSFDA,in1992,andresultsofitsuse to treat advanced RCC were already reported in 1995.