TGF-ß signaling and the interaction between platelets and T-cells in tumor microenvironment: Foes or friends?

T-cells, as the main immune cells in fighting against cancer cells, are usually overwhelmed by many factors. Tumor microenvironment (TME) changes are one of the factors that can limit T-cells functions. On the other hand, platelets which are known as the main source of transforming growth factor-ß (TGF-ß) in TME, are seemingly insignificant immune cells that can affect T-cell functions. There is a hypothesis that platelets might prevent tumor growth by stimulating cellular immunity, especially T-cells in pre-cancer status while they can inhibit T-cells and stimulate tumor growth in the advanced stage of cancer. Therefore, platelets could act as a double-edged sword in the activation of T-cells under pre-cancer and advanced stages of cancer conditions. In this review, the interaction between platelets and T cells in pre-cancer and advanced stages of cancer and the role of TGF-ß signaling in different stages of cancer will be discussed.

Primary Immunodeficiency and Thrombocytopenia.

Primary immunodeficiency (PID) or Inborn errors of immunity (IEI) refers to a heterogeneous group of disorders characterized by immune system impairment. Although patients with IEI manifest highly variable symptoms, the most common clinical manifestations are recurrent infections, autoimmunity and malignancies. Some patients present hematological abnormality including thrombocytopenia due to different pathogenic mechanisms. This review focuses on primary and secondary thrombocytopenia as a complication, which can occur in IEI. Based on the International Union of Immunological Societies phenotypic classification for IEI, the several innate and adaptive immunodeficiency disorders can lead to thrombocytopenia. This review, for the first time, describes manifestation, mechanism and therapeutic modalities for thrombocytopenia in different classes of IEI.

Breakfast-Based Dietary Patterns and Obesity in Tehranian Adults.

BACKGROUND: Breakfast is an important meal of the day that contributes to an overall healthy dietary pattern, better nutrient intake, and diet quality. This study sought to investigate the relationship between breakfast patterns and general and central obesity among middle-aged adults. METHODS: In this cross-sectional study of 840 apparently healthy women and men, aged 20-59 years, we assessed usual dietary intake by means of three 24-hour dietary recalls and we took anthropometric measurements. Dietary patterns were subsequently identified by factor analysis. To assess the association between breakfast composition and central and general obesity, logistic regression analysis was performed. RESULTS: We identified three major dietary patterns by factor analysis: the "bread and grains, meat products, and coffee" dietary pattern, the "sweets, tea and coffee" dietary pattern, and the "fruits, vegetables, and eggs" dietary pattern. Those people in the third tertile of the "sweets, tea and coffee" dietary category had a greater chance of having central obesity (odds ratio, 1.80; 95% confidence interval, 1.25-2.59; P=0.001). Moreover, higher adherence to the "bread and grains, meat products, and coffee" pattern increased the chance of central obesity (odds ratio, 1.67; 95% confidence interval, 1.47-1.97; P=0.03). CONCLUSION: Overall, our results suggest that specific breakfast dietary patterns are associated with increased odds of central obesity in Iranian adults.

Down-regulation of platelet adhesion receptors is a controlling mechanism of thrombosis, while also affecting post-transfusion efficacy of stored platelets.

Physiologically, upon platelet activation, uncontrolled propagation of thrombosis is prevented by regulating mechanisms which affect the expression and function of either platelet adhesion receptors or integrins. Receptor ectodomain shedding is an elective mechanism which is mainly involved in down-regulation of adhesion receptors GPIbα and GPVI. Platelet integrin αIIbß3 can also be modulated with a calpain-dependent proteolytic cleavage. In addition, activating signals may induce the internalization of expressed receptors to selectively down-regulate their intensity. Alternatively, further activation of platelets is associated with microvesiculation as a none-selective mechanism which leads to the loss of membrane- bearing receptors. In a non-physiological condition, the storage of therapeutic platelets has also shown to be associated with the unwilling activation of platelets which triggers receptors down-regulation via aforementioned different mechanisms. Notably, herein the changes are time-dependent and not controllable. While the expression and shedding of pro-inflammatory molecules can induce post-transfusion adverse effects, stored-dependent loss of adhesion receptors by ectodomain shedding or microvesiculation may attenuate post-transfusion adhesive functions of platelets causing their premature clearance from circulation. In its first part, the review presented here aims to describe the mechanisms involved in down-regulation of platelet adhesion receptors. It then highlights the crucial role of ectodomain shedding and microvesiculation in the propagation of "platelet storage lesion" which may affect the post-transfusion efficacy of platelet components.