RESUMO
This study was performed to gain further insight in the heterogeneity of monocytes in the different categories of acute coronary syndrome (ACS), especially between patients with unstable angina pectoris, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). For this purpose, blood samples were collected in the acute phase from patients presenting with an ACS. These samples were examined with multiparameter flow cytometry to identify the different monocyte subsets and to analyze the expression of monocyte-associated molecules. Leukocytes, as well as an absolute number of monocytes, showed a clear and significant increase in patients with STEMI. This increase was seen in all subtypes of monocytes. The classical monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased CD11b expression when compared to the control group, while these cells showed a decreased expression pattern in STEMI patients. This increased CD11b-expression was also seen in the intermediate monocytes of NSTEMI, while it was almost completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1, which is almost exclusively expressed on intermediate and nonclassical monocytes, showed a significant decrease in expression in patients with STEMI. In conclusion, intermediate and nonclassical monocytes have a different immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as target molecules for novel therapeutic strategies to diminish the migration of proinflammatory monocytes into the myocardial tissue. © 2017 International Society for Advancement of Cytometry.
Assuntos
Síndrome Coronariana Aguda/sangue , Angina Instável/sangue , Monócitos/metabolismo , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Síndrome Coronariana Aguda/patologia , Idoso , Idoso de 80 Anos ou mais , Angina Instável/patologia , Antígeno CD11b/sangue , Receptor 1 de Quimiocina CX3C/sangue , Receptor 1 de Quimiocina CX3C/genética , Diagnóstico Diferencial , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/patologiaRESUMO
Anti-PD1 and anti-PDL1 monotherapies have shown clinical efficacy in stage IV urothelial cancer and are integrated into current clinical practice. However, only a small number of the patients treated with single-agent checkpoint blockade experience an antitumour response. Insufficient priming or inhibitory factors in the tumour immune microenvironment might have a role in the lack of response. CTLA4 is an inhibitory checkpoint on activated T cells that is being studied as a therapeutic target in combination with anti-PD1 or anti-PDL1 therapies in advanced urothelial cancer. In locally advanced urothelial cancer, this combination approach has shown encouraging antitumour effects when administered pre-operatively. We believe that the presence of pre-existing intratumoural T cell immunity is not a prerequisite for response to combination therapy and that the additional value of CTLA4 blockade might involve the broadening of peripheral T cell priming, thereby transforming immunologically cold tumours into hot tumours.