Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Type 2 diabetes (T2D) is one of the leading causes of CV morbidity and mortality and accounts a significant social and financial burden of developed countries. CVD is often asymptomatic in diabetic patients and a high prevalence of silent coronary and brain ischemia have been reported in T2D. In addition, diabetes reduces the tolerance of target organs to ischemia and the efficacy of protective treatments. Current methods based on traditional CV risk factors only permit us to identify less than 50% of patients at risk of developing an acute ischemic event. Therefore, new strategies not only to better identify T2D patients at risk of CVD but also to reduce the consequences of ischemic events are urgently needed. This project has two major objectives: 1) To develop new methods for better identifying the subset of T2D patients at risk of ischemic events, thus impacting in prevention; and 2) To develop new therapeutic strategies to limit the consequences of ischemic events based on the study of the underlying mechanisms. Our participation in this integrated and multidisciplinary study is aimed to determine whether the presence of specific subsets of circulating monocytes in T2D patients could be associated to the development of CVD.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Type 2 diabetes (T2D) is one of the leading causes of CV morbidity and mortality and accounts a significant social and financial burden of developed countries. CVD is often asymptomatic in diabetic patients and a high prevalence of silent coronary and brain ischemia have been reported in T2D. In addition, diabetes reduces the tolerance of target organs to ischemia and the efficacy of protective treatments. Current methods based on traditional CV risk factors only permit us to identify less than 50% of patients at risk of developing an acute ischemic event. Therefore, new strategies not only to better identify T2D patients at risk of CVD but also to reduce the consequences of ischemic events are urgently needed. This project has two major objectives: 1) To develop new methods for better identifying the subset of T2D patients at risk of ischemic events, thus impacting in prevention; and 2) To develop new therapeutic strategies to limit the consequences of ischemic events based on the study of the underlying mechanisms. Our participation in this integrated and multidisciplinary study is aimed to determine whether the presence of specific subsets of circulating monocytes in T2D patients could be associated to the development of CVD.

Metastatic renal cell carcinoma RCC is one of the cancers where the new immunotherapy approach is generating more expectations and hope. For instance, treatment with agents able to block the interaction of the PDL1 with PD-1 produced durable responses in ~30% of patients with ccRCC. Unfortunately, an important limitation of those treatments is the fairly small proportion of patients who achieve clinical responses. In this context, the search for new immune checkpoints appears to be a necessity in order to increase the number of patients that could benefit of immunotherapy treatments. ccRCC tumors overexpressing TIM-1 become engaged in the expression of a repertoire of molecules that favor tumor growth, apoptosis inhibition, angiogenesis, invasion and immune evasion. TIM-1 ectodomain shedding favors transcription of IL-6 and IL-11, and promotes further activation of the gp130/STAT3 pathway, by mechanisms that remain to be described both in tumor and surrounding cells. In addition, as far as TIM-1 is expressed constitutively by T lymphocytes, the shedded form of TIM-1 produced by ccRCC tumor cells could act as a decoy receptor blocking the function of this receptor in lymphopcytes. Detailed analysis of the impact of TIM-1 expression in tumor progression and host immune system is clearly needed since it shall improve our knowledge on ccRCC tumor biology and hopefully provide novel targets for effective and personalized treatment of ccRCC patients.

Metastatic renal cell carcinoma RCC is one of the cancers where the new immunotherapy approach is generating more expectations and hope. For instance, treatment with agents able to block the interaction of the PDL1 with PD-1 produced durable responses in ~30% of patients with ccRCC. Unfortunately, an important limitation of those treatments is the fairly small proportion of patients who achieve clinical responses. In this context, the search for new immune checkpoints appears to be a necessity in order to increase the number of patients that could benefit of immunotherapy treatments. ccRCC tumors overexpressing TIM-1 become engaged in the expression of a repertoire of molecules that favor tumor growth, apoptosis inhibition, angiogenesis, invasion and immune evasion. TIM-1 ectodomain shedding favors transcription of IL-6 and IL-11, and promotes further activation of the gp130/STAT3 pathway, by mechanisms that remain to be described both in tumor and surrounding cells. In addition, as far as TIM-1 is expressed constitutively by T lymphocytes, the shedded form of TIM-1 produced by ccRCC tumor cells could act as a decoy receptor blocking the function of this receptor in lymphopcytes. Detailed analysis of the impact of TIM-1 expression in tumor progression and host immune system is clearly needed since it shall improve our knowledge on ccRCC tumor biology and hopefully provide novel targets for effective and personalized treatment of ccRCC patients.