TABATHA GUTIERREZ PRIETO MARTINS ROCHA

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LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina

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  • article 10 Citação(ões) na Scopus
    Variants in Epithelial-Mesenchymal Transition and Immune Checkpoint Genes Are Associated With Immune Cell Profiles and Predict Survival in Non-Small Cell Lung Cancer
    (2020) PARRA, Edwin Roger; JIANG, Mei; MACHADO-RUGOLO, Juliana; YAEGASHI, Lygia Bertalha; PRIETO, Tabatha; FARHAT, Cecilia; SA, Vanessa Karen de; NAGAI, Maria Aparecida; LIMA, Vladmir Claudio Cordeiro de; TAKAGAKI, Tereza; TERRA, Ricardo; FABRO, Alexandre Todorovic; CAPELOZZI, Vera Luiza
    Context.-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.
  • article 11 Citação(ões) na Scopus
    Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value
    (2020) BALANCIN, Marcelo Luiz; TEODORO, Walcy Rosolia; BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; FARHAT, Cecilia; VELOSA, Ana Paula; SOUZA, Paola da Costa; YAEGASHI, Lygia Bertalha; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa Yae; CAPELOZZI, Vera Luiza
    Previous studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V <= 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.