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Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes

Cancer 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 i...

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Autores principales: Gil-Julio, Hernani, Perea, Francisco, Rodriguez-Nicolas, Antonio, Cozar, Jose Manuel, González-Ramirez, Amanda Rocío, Concha, Angel, Garrido, Federico, Aptsiauri, Natalia, Ruiz-Cabello, Francisco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307653/
https://www.ncbi.nlm.nih.gov/pubmed/34298868
http://dx.doi.org/10.3390/ijms22147248
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author Gil-Julio, Hernani
Perea, Francisco
Rodriguez-Nicolas, Antonio
Cozar, Jose Manuel
González-Ramirez, Amanda Rocío
Concha, Angel
Garrido, Federico
Aptsiauri, Natalia
Ruiz-Cabello, Francisco
author_facet Gil-Julio, Hernani
Perea, Francisco
Rodriguez-Nicolas, Antonio
Cozar, Jose Manuel
González-Ramirez, Amanda Rocío
Concha, Angel
Garrido, Federico
Aptsiauri, Natalia
Ruiz-Cabello, Francisco
author_sort Gil-Julio, Hernani
collection PubMed
description Cancer 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.
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spelling pubmed-83076532021-07-25 Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes Gil-Julio, Hernani Perea, Francisco Rodriguez-Nicolas, Antonio Cozar, Jose Manuel González-Ramirez, Amanda Rocío Concha, Angel Garrido, Federico Aptsiauri, Natalia Ruiz-Cabello, Francisco Int J Mol Sci Article Cancer 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. MDPI 2021-07-06 /pmc/articles/PMC8307653/ /pubmed/34298868 http://dx.doi.org/10.3390/ijms22147248 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gil-Julio, Hernani
Perea, Francisco
Rodriguez-Nicolas, Antonio
Cozar, Jose Manuel
González-Ramirez, Amanda Rocío
Concha, Angel
Garrido, Federico
Aptsiauri, Natalia
Ruiz-Cabello, Francisco
Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title_full Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title_fullStr Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title_full_unstemmed Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title_short Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes
title_sort tumor escape phenotype in bladder cancer is associated with loss of hla class i expression, t-cell exclusion and stromal changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307653/
https://www.ncbi.nlm.nih.gov/pubmed/34298868
http://dx.doi.org/10.3390/ijms22147248
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