Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy
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2022
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| _version_ | 1866901143848747008 |
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| author | Ramos Paradas, Javier Garrido-Martín, Eva María |
| author_facet | Ramos Paradas, Javier Garrido-Martín, Eva María |
| contents | <p><em>Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung</em></p> <p><em>cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors</em></p> <p><em>has shown outstanding results in NSCLC, the precise identification of responders remains a major</em></p> <p><em>challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas</em></p> <p><em>or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics</em></p> <p><em>of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined.</em></p> <p><em>We hypothesized that specific molecular aberrations may impact the immune microenvironment</em></p> <p><em>in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant</em></p> <p><em>to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify</em></p> <p><em>robust predictive biomarkers and improve potential benefits from immunotherapy. We established</em></p> <p><em>a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features</em></p> <p><em>were comprehensively characterized by genomic and immune-targeted sequencing panels along</em></p> <p><em>with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel</em></p> <p><em>subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed</em></p> <p><em>higher immune infiltration and upregulated genes involved in potentiating immune responses</em></p> <p><em>when compared to pro-tumorigenic samples, which favored tumoral progression. This classification</em></p> <p><em>identified a set of biomarkers that could potentially predict response to immunotherapy. These results</em></p> <p><em>could improve patient selection and expand potential benefits from immunotherapy.</em></p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_3390_jcm11061500 |
| institution | Zenodo |
| language | |
| publishDate | 2022 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy Ramos Paradas, Javier Garrido-Martín, Eva María <p><em>Lung cancer is the leading cause of cancer mortality worldwide, with non-small cell lung</em></p> <p><em>cancer (NSCLC) being the most prevalent histology. While immunotherapy with checkpoint inhibitors</em></p> <p><em>has shown outstanding results in NSCLC, the precise identification of responders remains a major</em></p> <p><em>challenge. Most studies attempting to overcome this handicap have focused on adenocarcinomas</em></p> <p><em>or squamous cell carcinomas. Among NSCLC subtypes, the molecular and immune characteristics</em></p> <p><em>of lung large cell carcinoma (LCC), which represents 10% of NSCLC cases, are not well defined.</em></p> <p><em>We hypothesized that specific molecular aberrations may impact the immune microenvironment</em></p> <p><em>in LCC and, consequently, the response to immunotherapy. To that end, it is particularly relevant</em></p> <p><em>to thoroughly describe the molecular genotype–immunophenotype association in LCC–to identify</em></p> <p><em>robust predictive biomarkers and improve potential benefits from immunotherapy. We established</em></p> <p><em>a cohort of 18 early-stage, clinically annotated, LCC cases. Their molecular and immune features</em></p> <p><em>were comprehensively characterized by genomic and immune-targeted sequencing panels along</em></p> <p><em>with immunohistochemistry of immune cell populations. Unbiased clustering defined two novel</em></p> <p><em>subgroups of LCC. Pro-immunogenic tumors accumulated certain molecular alterations, showed</em></p> <p><em>higher immune infiltration and upregulated genes involved in potentiating immune responses</em></p> <p><em>when compared to pro-tumorigenic samples, which favored tumoral progression. This classification</em></p> <p><em>identified a set of biomarkers that could potentially predict response to immunotherapy. These results</em></p> <p><em>could improve patient selection and expand potential benefits from immunotherapy.</em></p> |
| title | Comprehensive Characterization of Human Lung Large Cell Carcinoma Identifies Transcriptomic Signatures with Potential Implications in Response to Immunotherapy |
| url | https://doi.org/10.3390/jcm11061500 |