ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Evolution of Genomic and T-cell Repertoire Heterogeneity of Malignant Pleural Mesothelioma Under Dasatinib Treatment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Innovative approaches for lung cancer screening and interception.Nature reviews. Clinical oncology · 2026Review
- Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.Frontiers in oncology · 2026Review
- Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception.Cancer cell · 2025Article
- Telomere-related gene risk model predicts prognostic and immune microenvironment alterations in prostate cancer.Scientific reports · 2025Article
- Multiregional transcriptomic profiling provides improved prognostic insight in localized non-small cell lung cancer.NPJ precision oncology · 2024Article
- Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.Thoracic cancer · 2024Article
- Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2023Article
- Globally shared TCR repertoires within the tumor-infiltrating lymphocytes of patients with metastatic gynecologic cancer.Scientific reports · 2023Article
- Multiplatform Analysis of Intratumoral PTEN Heterogeneity in Melanoma.The Journal of investigative dermatology · 2023Article
- Tumor-infiltrating lymphocytes are functionally inactivated by CD90+ stromal cells and reactivated by combined Ibrutinib and Rapamycin in human pleural mesothelioma.Theranostics · 2022Article
- Intratumor heterogeneity: the hidden barrier to immunotherapy against MSI tumors from the perspective of IFN-γ signaling and tumor-infiltrating lymphocytes.Journal of hematology & oncology · 2021Review
- Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma.Genome medicine · 2021Article
- Article
- Review
- The Prognostic Value and Immune Landscapes of a mFrontiers in cell and developmental biology · 2021Article
- Challenges in lung and thoracic pathology: molecular advances in the classification of pleural mesotheliomas.Virchows Archiv : an international journal of pathology · 2021Review
- Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
Abstract
purposeMalignant pleural mesothelioma (MPM) is considered an orphan disease with few treatment options. Despite multimodality therapy, the majority of MPMs recur and eventually become refractory to any systemic treatment. One potential mechanism underlying therapeutic resistance may be intratumor heterogeneity (ITH), making MPM challenging to eradicate. However, the ITH architecture of MPM and its clinical impact have not been well studied. EXPERIMENTAL
designWe delineated the immunogenomic ITH by multiregion whole-exome sequencing and T-cell receptor (TCR) sequencing of 69 longitudinal MPM specimens from nine patients with resectable MPM, who were treated with dasatinib.
resultsThe median total mutation burden before dasatinib treatment was 0.65/Mb, similar with that of post-dasatinib treatment (0.62/Mb). The median proportion of mutations shared by any given pair of two tumor regions within the same tumors was 80% prior to and 83% post-dasatinib treatment indicating a relatively homogenous genomic landscape. T-cell clonality, a parameter indicating T-cell expansion and reactivity, was significantly increased in tumors after dasatinib treatment. Furthermore, on average, 82% of T-cell clones were restricted to individual tumor regions, with merely 6% of T-cell clones shared by all regions from the same tumors indicating profound TCR heterogeneity. Interestingly, patients with higher T-cell clonality and higher portion of T cells present across all tumor regions in post-dasatinib-treated tumors had significantly longer survival.
conclusionsDespite the homogeneous genomic landscape, the TCR repertoire is extremely heterogeneous in MPM. Dasatinib may potentially induce T-cell response leading to improved survival.
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