Cancer-associated inflammation: pathophysiology and clinical significance.

PURPOSE: Cancer cells, despite stemming from the own cells of their host, usually elicit an immune response. This response usually enables elimination of cancer at its earliest stages. However, some tumors develop mechanisms of escaping immune destruction and even profiting from tumor-derived inflammation. METHODS: We summarized the roles of different immune cell populations in various processes associated with cancer progression and possible methods of reshaping tumor-associated inflammation to increase the efficacy of cancer therapy. RESULTS: Changes in various signaling pathways result in attraction of immunosuppressive, pro-tumorigenic cells, such as myeloid-derived suppressor cells, tumor-associated macrophages, and neutrophils, while at the same time suppressing the activity of lymphocytes, which have the potential of destroying cancer cells. These changes promote tumor progression by increasing angiogenesis and growth, accelerating metastasis, and impairing drug delivery to the tumor site. CONCLUSION: Due to its multi-faceted role in cancer, tumor-associated inflammation can serve as a valuable therapy target. By increasing it, whether through decreasing overall immunosuppression with immune checkpoint inhibitor therapy or through more specific methods, such as cancer vaccines, oncolytic viruses, or chimeric antigen receptor T cells, cancer-derived immunosuppression can be overcome, resulting in immune system destroying cancer cells. Even changes occurring in the microbiota can influence the shape of antitumor response, which could provide new attractive diagnostic or therapeutic methods. Interestingly, also decreasing the distorted tumor-associated inflammation with non-steroidal anti-inflammatory drugs can lead to positive outcomes.

Antiplatelet Effects of PCSK9 Inhibitors in Primary Hypercholesterolemia.

Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.