Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.

Sphingosine-1-phosphate (S1P), a bioactive lipid, plays important roles in tumor development through its ability to promote tumor cell growth, migration, and invasion. S1P, synthesized by sphingosine kinase 1 and 2 (SK1 and SK2), can initiate multiple signal events through intracellular and extracellular mechanisms. In human cancer patients, increased levels of S1P and SK1 are correlated with poor prognosis and high incidence of diseases recurrence. How sphingolipid signaling regulates the function of immune cells and inflammation during tumor development remains poorly understood. Our results demonstrate that sphingolipid-induced inflammasome activation and IL-1β production promotes tumorigenesis and metastasis. Interestingly, our data indicate that SK-1/S1P signaling induces inflammasome activation and IL-1 production. We found that in MMTV-PyT transgenic mouse mammary gland tumor model, genetic loss of SphK1 significantly inhibited breast cancer progression and metastasis, accompanied by reduced levels of IL-1β at primary tumors and metastatic sites. Our results further show that SK1 and S1P modulate tumor microenvironments through induction of inflammasome activation and recruitment of myeloid cells. These findings indicate that the cross-talk between the SK1/S1P and inflammasome/IL-1 pathways promotes tumor growth and metastasis.

Moyamoya disease (MMD) is a rare occlusive cerebrovascular disease that is characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches with compensatory development of dilated and fragile collateral vasculature at the base of the brain. MMD has a bimodal age distribution commonly affecting children and adults, whereas onset in the elderly population is a rare occurrence. Here, we present a case of a 78-year-old patient of Indonesian descent who was incidentally found to have moyamoya arteriopathy after presenting with acute ischemic stroke in the left pons. The patient underwent diagnostic cerebral angiogram that showed right middle cerebral artery stenosis with pathognomonic collateral moyamoya vessels. The patient was discharged on antiplatelet therapy. We report a rare case of an elderly patient with MMD. The role of medical or surgical management in asymptomatic MMD in elderly patients remains largely unknown.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome characterized by a pathologic immune response in the setting of infection, malignancy, acute illness, or any immunological stimulus. Infection is the most common etiology of HLH. HLH involves aberrant activation of lymphocytes and macrophages with resultant hypercytokinemia due to an inappropriately stimulated and ineffective immune response. Here, we present the case of a previously healthy 19-year-old male presenting with hiccups and scleral icterus, who was found to have HLH due to a severe Epstein-Barr virus infection. Despite a morphologically normal bone marrow biopsy, the patient met the diagnostic criteria for HLH, including a low natural killer cell count and elevated soluble interleukin-2 receptor. Notably, ferritin was severely elevated at 85,810 ng/mL. The patient was treated with an induction course of dexamethasone intravenously for eight weeks. Since HLH can progress into multi-organ failure, timely diagnosis and prompt initiation of treatment are critical. Novel disease-modifying therapies and further clinical trials are warranted to treat this potentially fatal immunological disease with multisystem ramifications.