Clear cell renal cell carcinoma (ccRCC) has shown durable responses to checkpoint blockade therapies. However, important gaps persist in the understanding of its immune microenvironment. This study ...aims to investigate the expression and prognostic significance of immune checkpoints in primary and metastatic ccRCC, in relation with mature dendritic cells (DC) and T-cell densities.
We investigated the infiltration and the localization of CD8(+) T cells and mature DC, and the expression of immune checkpoints (PD-1, LAG-3, PD-L1, and PD-L2) in relation with prognosis, in 135 primary ccRCC tumors and 51 ccRCC lung metastases. RNA expression data for 496 primary ccRCC samples were used as confirmatory cohort.
We identify two groups of tumors with extensive CD8(+) T-cell infiltrates. One group, characterized by high expression of immune checkpoints in the absence of fully functional mature DC, is associated with increased risk of disease progression. The second group, characterized by low expression of immune checkpoints and localization of mature DC in peritumoral immune aggregates (tertiary lymphoid structures), is associated with good prognosis.
The expression of the immune checkpoints and the localization of DC in the tumor microenvironment modulate the clinical impact of CD8(+) T cells in ccRCC.
Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes
. The clinical presentation of patients with different subtypes is often atypical, and ...responses to therapies such as immune checkpoint blockade vary widely
. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8
T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases.
Este artigo é fruto de reflexões realizadas por educadoras durante o exercício docente em curso de Licenciatura em Pedagogia. Tem como objetivo discutir a relação entre a visão de Paulo Freire ...considerando a importância da percepção da realidade política e social pelo educando, as práticas voltadas para o processo de de construção do conhecimento e os estudos sobre a aprendizagem significativa na visão de David Ausubel. As educadoras, relacionam o pensamento dos teóricos dialogando com a importância do aluno aprender a partir da apresentação de um conteúdo significativo específico considerando o contexto cultural e educacional constantes no seu cotidiano, vinculados à efetiva aprendizagem e atuação no espaço social e profissional. O presente estudo foi realizado pautado em pesquisa bibliográfica. Conclui-se que a aprendizagem significativa, alicerça a construção do conhecimento humano e o faz integrando pensamentos, sentimentos e ações, conduzindo ao engrandecimento pessoal e social.
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