Graphical abstract

Key Points The synthetic retinoid ST1926 induces apoptosis of ATL cells and prolongs survival of ATL mice. At the molecular level, ST1926 causes early DNA damage, upregulates p53, and downregulates Tax expression.

Pyroptosis is a newly discovered programmed cell death with inflammasome formation. Pattern recognition receptors that identify repetitive motifs of prospective pathogens such as LPS of gram‐negative bacteria are crucial to pyroptosis. Upon stimulation by pathogen‐associated molecular patterns or damage‐associated molecular patterns, proinflammatory cytokines, mainly IL‐1 family members IL‐1β and IL‐18, are released through pyroptosis specific pore‐forming protein, gasdermin D. Even though IL‐1 family members are mainly involved in innate immunity, they can be factors in adaptive immunity. Given the importance of IL‐1 family members in health and diseases, deciphering the role of pyroptosis in the regulation of innate and adaptive immunity is of great importance, especially with the recent progress in identifying the exact mechanism of such a pathway. In this review, we will focus on how the innate inflammatory mediators can regulate the adaptive immune system and vice versa via pyroptosis.

The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

Acute respiratory distress syndrome (ARDS) is a major complication of the respiratory illness coronavirus disease 2019, with a death rate reaching up to 40%. The main underlying cause of ARDS is a cytokine storm that results in a dysregulated immune response. This review discusses the role of cytokines and chemokines in SARS-CoV-2 and its predecessors SARS-CoV and MERS-CoV, with particular emphasis on the elevated levels of inflammatory mediators that are shown to be correlated with disease severity. For this purpose, we reviewed and analyzed clinical studies, research articles, and reviews published on PubMed, EMBASE, and Web of Science. This review illustrates the role of the innate and adaptive immune responses in SARS, MERS, and COVID-19 and identifies the general cytokine and chemokine profile in each of the three infections, focusing on the most prominent inflammatory mediators primarily responsible for the COVID-19 pathogenesis. The current treatment protocols or medications in clinical trials were reviewed while focusing on those targeting cytokines and chemokines. Altogether, the identified cytokines and chemokines profiles in SARS-CoV, MERS-CoV, and SARS-CoV-2 provide important information to better understand SARS-CoV-2 pathogenesis and highlight the importance of using prominent inflammatory mediators as markers for disease diagnosis and management. Our findings recommend that the use of immunosuppression cocktails provided to patients should be closely monitored and continuously assessed to maintain the desirable effects of cytokines and chemokines needed to fight the SARS, MERS, and COVID-19. The current gap in evidence is the lack of large clinical trials to determine the optimal and effective dosage and timing for a therapeutic regimen.