PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis
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RESEARCH
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PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis Katia R M Leite1,2*, Sabrina T. Reis1, José Pontes Junior1, Marcelo Zerati1, Daniel de Oliveira Gomes1, Luiz H. Camara-Lopes2 and Miguel Srougi1
Abstract Background: PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition of the tumor-directed T-cell immune response. There are few reports in the literature evaluating PD-L1 expression in association to prognosis specifically in renal cell cancer clear cell type (RCC-CC). Methods: Immunohistochemistry using a PD-L1 polyclonal antibody was performed on a tissue microarray (TMA) that contained 115 surgical specimens of RCC-CC. Cases were classified based on the absence or presence of staining intensity in the cytoplasm and membranes of the tumor cells. Statistical analysis was used to determine the association of PD-L1 expression with classic prognostic factors and tumor recurrence. Results: PD-L1 expression was positive in 56.5 % of tumors. The univariate analysis showed a correlation between PD-L1 expression and nuclear Fuhrman grade (p = 0.021) and microvascular tumor embolization (p = 0.039). One hundred and four patients were monitored for a mean time of 115.7 months. Seventeen patients (16.3 %) suffered tumor recurrence. Negative outcomes were associated with higher nuclear grade tumors, PD-L1 expression, and the presence of microvascular invasion. Conclusion: Our findings confirm that PD-L1 expression is an important prognostic factor in RCC-CC. Keywords: Renal cell cancer, PD-L1, Prognosis, Immunotherapy, Immunohistochemistry
Background Recently, the capacity of neoplastic cells to evade immunological destruction became an additional checkpoint in assessing the hallmarks of cancer [1]. T cells play the most important role in this context; the recognition of tumorassociated antigens by healthy T cells allows the activation of a specific anti-tumor immune reaction. CD8+ effector T cells, known as cytotoxic T lymphocytes (CTLs), are the main players in this process. Two receptors, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD-1), have been actively studied in cancer for their potential roles as inhibitory receptors. Blockage of these receptors by antibodies has been studied in numerous clinical trials with promising results [2, 3]. * Correspondence: [email protected] 1 Department of Urology, Laboratory of Medical Research, University of São Paulo Medical School, Sao Paulo, Brazil 2 Department of Molecular Biology, Genoa Biotecnologia SA, Av Dr. Arnaldo #455, room 2145, 01246-903 Sao Paulo, Brazil
PD-1 is a 288-amino acid cell-surface protein. PD-1 binds two ligands, PD-L1 and PD-L2, which negatively regulate the immune response. The expression of PD-L1 (also known as B7-H1) on tumor cells leads to the inhibition of the T cell-mediated immune respo
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