title: The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture.
abstract: Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I) expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/"soft" or irreversible/"hard" due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL).
authors.affiliation: Servicio de Analisis Clinicos e Inmunologia, UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. federico.garrido.sspa@juntadeandalucia.es.|Instituto de Investigacion Biosanitaria ibs.Granda, Granada 18014, Spain. federico.garrido.sspa@juntadeandalucia.es.|Departamento de Bioquimica, Biologia Molecular e Inmunologia III, Facultad de Medicina, Universidad de Granada, Granada 18071, Spain. federico.garrido.sspa@juntadeandalucia.es.
authors.forename: Federico
authors.initials: F
authors.lastname: Garrido
authors.affiliation: Servicio de Analisis Clinicos e Inmunologia, UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. franjapega@correo.ugr.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Perea
authors.affiliation: Servicio de Analisis Clinicos e Inmunologia, UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. monicabernals@hotmail.com.
authors.forename: Mónica
authors.initials: M
authors.lastname: Bernal
authors.affiliation: Unidad de Cirugía Torácica, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. abelsapara@hotmail.com.
authors.forename: Abel
authors.initials: A
authors.lastname: Sánchez-Palencia
authors.affiliation: Instituto de Investigacion Biosanitaria ibs.Granda, Granada 18014, Spain. naptsiauri@ugr.es.|Departamento de Bioquimica, Biologia Molecular e Inmunologia III, Facultad de Medicina, Universidad de Granada, Granada 18071, Spain. naptsiauri@ugr.es.
authors.forename: Natalia
authors.initials: N
authors.lastname: Aptsiauri
authors.affiliation: Servicio de Analisis Clinicos e Inmunologia, UGC Laboratorio Clinico, Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. fruizc@ugr.es.|Instituto de Investigacion Biosanitaria ibs.Granda, Granada 18014, Spain. fruizc@ugr.es.|Departamento de Bioquimica, Biologia Molecular e Inmunologia III, Facultad de Medicina, Universidad de Granada, Granada 18071, Spain. fruizc@ugr.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Cabello
keywords: HLA class I loss; tumor immune escape; tumor infiltrating lymphocytes (TILs)