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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8307653 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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