Gil-Julio, HernaniPerea, FranciscoRodriguez-Nicolas, AntonioCozar, Jose ManuelGonzález-Ramirez, Amanda RocíoConcha, AngelGarrido, FedericoAptsiauri, NataliaRuiz-Cabello, Francisco2022-03-212022-03-212021-07-06Gil-Julio H, Perea F, Rodriguez-Nicolas A, Cozar JM, González-Ramirez AR, Concha A, et al. Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes. Int. J. Mol. Sci. 2021, 22, 7248.http://hdl.handle.net/10668/3478Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors.enAttribution-NonCommercial-NoDerivatives 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Bladder cancerHLA class ICancer immune escapeTILsT-cell exclusionPD-L1Cancer associated fibroblastsNeoplasias de la vejiga urinariaAntígeno HLA-A1Fibroblastos asociados al cáncerAntígeno B7-H1Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and overMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Sexuality::Homosexuality::Homosexuality, FemaleMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::Histocompatibility Antigens Class IMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunotherapy, ActiveMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocytes, Tumor-InfiltratingMedical Subject Headings::Persons::Persons::Men::Nurses, MaleMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::EndophenotypesMedical Subject Headings::Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::T-Lymphocyte Subsets::T-Lymphocytes, CytotoxicMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Tumor EscapeMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cellular Microenvironment::Tumor MicroenvironmentMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Urologic Neoplasms::Urinary Bladder NeoplasmsMedical Subject Headings::Persons::Persons::Age Groups::Adult::Young Adultresearch article34298868open access10.3390/ijms221472481422-0067PMC8307653