Immunological landscape and immunotherapy of hepatocellular carcinoma.
Advanced hepatocellular carcinoma (HCC) is a serious therapeutic challenge and targeted therapies only provide a modest benefit in terms of overall survival. Novel approaches are urgently needed for the treatment of this prevalent malignancy. Evidence demonstrating the antigenicity of tumour cells, the discovery that immune checkpoint molecules have an essential role in immune evasion of tumour cells, and the impressive clinical results achieved by blocking these inhibitory receptors, are revolutionizing cancer immunotherapy. Here, we review the data on HCC immunogenicity, the mechanisms for HCC immune subversion and the different immunotherapies that have been tested to treat HCC. Taking into account the multiplicity of hyperadditive immunosuppressive forces acting within the HCC microenvironment, a combinatorial approach is advised. Strategies include combinations of systemic immunomodulation and gene therapy, cell therapy or virotherapy.
Department of Medicine, Clinica Universidad de Navarra and Centre for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII, 31080 Pamplona, Spain.
Jesús
J
Prieto
Department of Oncology, Clinica Universidad de Navarra and Centre for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII, 31080 Pamplona, Spain.
Ignacio
I
Melero
Liver Unit, Clinica Universidad de Navarra and Centre for Applied Medical Research (CIMA), University of Navarra, Avenida Pio XII, 31080 Pamplona, Spain. CIBERehd, Instituto de Salud Carlos III, Monforte de Lemos 3-5, Avenida Pio XII, 28029 Madrid, Spain.
Bruno
B
Sangro
D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000276:immunology* / Q000628:therapy*