Variants in Epithelial-Mesenchymal Transition and Immune Checkpoint Genes Are Associated With Immune Cell Profiles and Predict Survival in Non-Small Cell Lung Cancer

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Autor(es): dc.contributorUniv Texas MD Anderson Canc Ctr-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorAC Camargo Canc Ctr-
Autor(es): dc.contributorInst Canc Sao Paulo-
Autor(es): dc.creatorParra, Edwin Roger-
Autor(es): dc.creatorJiang, Mei-
Autor(es): dc.creatorMachado-Rugolo, Juliana-
Autor(es): dc.creatorYaegashi, Lygia Bertalha-
Autor(es): dc.creatorPrieto, Tabatha-
Autor(es): dc.creatorFarhat, Cecilia-
Autor(es): dc.creatorSa, Vanessa Karen de [UNESP]-
Autor(es): dc.creatorNagai, Maria Aparecida [UNESP]-
Autor(es): dc.creatorCordeiro de Lima, Vladmir Claudio-
Autor(es): dc.creatorTakagaki, Tereza-
Autor(es): dc.creatorTerra, Ricardo-
Autor(es): dc.creatorFabro, Alexandre Todorovic-
Autor(es): dc.creatorCapelozzi, Vera Luiza-
Data de aceite: dc.date.accessioned2022-02-22T00:56:52Z-
Data de disponibilização: dc.date.available2022-02-22T00:56:52Z-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2021-06-25-
Data de envio: dc.date.issued2020-10-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.5858/arpa.2019-0419-OA-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/209539-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/209539-
Descrição: dc.descriptionContext.-Identification of gene mutations that are indicative of epithelial-mesenchymal transition and a noninflammatory immune phenotype may be important for predicting response to immune checkpoint inhibitors. Objective.-To evaluate the utility of multiplex immunofluorescence for immune profiling and to determine the relationships among tumor immune checkpoint and epithelial-mesenchymal transition genomic profiles and the clinical outcomes of patients with nonmetastatic non-small cell lung cancer. Design.-Tissue microarrays containing 164 primary tumor specimens from patients with stages I to IIIA non-small cell lung carcinoma were examined by multiplex immunofluorescence and image analysis to determine the expression of programmed death ligand-1 (PD-L1) on malignant cells, CD68; macrophages, and cells expressing the immune markers CD3, CD8, CD57, CD45RO, FOXP3, PD-1, and CD20. Immune phenotype data were tested for correlations with clinicopathologic characteristics, somatic and germline genetic variants, and outcome. Results.-A high percentage of PD-L1(+) malignant cells was associated with clinicopathologic characteristics, and high density of CD3+PD-1(+) T cells was associated with metastasis, suggesting that these phenotypes may be clinically useful to identify patients who will likely benefit from immunotherapy. We also found that ZEB2 mutations were a proxy for immunologic ignorance and immune tolerance microenvironments and may predict response to checkpoint inhibitors. A multivariate Cox regression model predicted a lower risk of death for patients with a high density of CD3(+)CD45RO(+) memory T cells, carriers of allele G of CTLA4 variant rs231775, and those whose tumors do not have ZEB2 mutations. Conclusions.-Genetic variants in epithelial mesenchymal transition and immune checkpoint genes are associated with immune cell profiles and may predict patient outcomes and response to immune checkpoint blockade.-
Descrição: dc.descriptionUniversity of Texas Lung Cancer Specialized Programs of Research Excellence-
Descrição: dc.descriptionFoundation for the Support of Research of the State of Sao Paulo-
Descrição: dc.descriptionUniv Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, 1515 Holcombe Blvd,Unit 951, Houston, TX 77030 USA-
Descrição: dc.descriptionUniv Sao Paulo, Fac Med, Dept Pathol & Lab Genom & Histomorphometry, Sao Paulo, SP, Brazil-
Descrição: dc.descriptionUniv Sao Paulo, Fac Med, Div Pneumol, Heart Inst Incor, Sao Paulo, Brazil-
Descrição: dc.descriptionSao Paulo State Univ, Clin Hosp, Fac Med, Dept Oncol, Sao Paulo, Brazil-
Descrição: dc.descriptionAC Camargo Canc Ctr, Med Oncol Dept, Sa Paulo, Brazil-
Descrição: dc.descriptionAC Camargo Canc Ctr, Translat Immune Oncol Grp, Sa Paulo, Brazil-
Descrição: dc.descriptionInst Canc Sao Paulo, Dept Thorac Surg, Sao Paulo, Brazil-
Descrição: dc.descriptionHeart Inst Incor, Dept Thorac Surg, Sao Paulo, Brazil-
Descrição: dc.descriptionUniv Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol & Legal Med, Ribeirao Preto, Brazil-
Descrição: dc.descriptionSao Paulo State Univ, Clin Hosp, Fac Med, Dept Oncol, Sao Paulo, Brazil-
Descrição: dc.descriptionUniversity of Texas Lung Cancer Specialized Programs of Research Excellence: P50CA70907-
Descrição: dc.descriptionFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2013/14277-4-
Descrição: dc.descriptionFoundation for the Support of Research of the State of Sao Paulo: FAPESP 2018-20403-6-
Formato: dc.format1234-1244-
Idioma: dc.languageen-
Publicador: dc.publisherColl Amer Pathologists-
Relação: dc.relationArchives Of Pathology & Laboratory Medicine-
???dc.source???: dc.sourceWeb of Science-
Título: dc.titleVariants in Epithelial-Mesenchymal Transition and Immune Checkpoint Genes Are Associated With Immune Cell Profiles and Predict Survival in Non-Small Cell Lung Cancer-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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