-
Cisplatin chemotherapy resistance revealed: TAMs release CCL22 as the culprit!
Tumor surrounding stromal cells, including tumor-associated macrophages (TAMs),crosstalk with the cancer cells to promote oncogenesis, tumor malignant progression, and drug resistance. Esophageal squamous cell carcinoma (ESCC) is among the deadliest types of solid tumors, with the extremely low 5-year overall survival (OS) rate, due to the high recurrence after chemotherapy. Cisplatin is widely used as a standard chemotherapy to treat ESCC patients; however, a plethora of patients suffer from chemoresistance. TAMs-secreted non-cellular substances, such as cytokines, growth factors, or non-coding RNA, function as important factors to provide a permissive microenvironment for tumor growt......
-
Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis
Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis promoting effects of cisplatin on ESCC cells. Mechanistically, CCL22 stimulated intratumoral diacylglycerol kinase α (DGKα) to produce phosphatidic acid (PA), which suppressed the activity of NADPH oxidase 4 (NOX4) and then blocked the overproduction of intratumoral reactive species oxy......
-
Targeting Erbin-mitochondria axis in platelets/ megakaryocytes promotes B cell-mediated antitumor immunity
The roles of platelets/megakaryocytes (MKs), the key components in the blood system,in the tumor microenvironment and antitumor immunity are unclear. In patients withcolorectal cancer, the number of platelets was significantly increased in patientswith metastasis, and Erbin expression was highly expressed in platelets from patientswith metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasisin mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient plateletshave increasing mitochondrial oxidative phosphorylation and secrete lipid metaboliteslike acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM.Notably, Acar en......
-
Frontier research on heart regeneration: challenging traditional concepts and reshaping miracles of injured hearts
For decades the common dogma was that the adult heart is incapable of regenerating lost myocardium after injury. In response to cardiac injury, adult mammals—including humans—fail to regenerate the majority of the lost cardiomyocytes and instead replace necrotic muscle with scar tissue. The loss of cardiomyocytes eventually compromises contractility of the remaining myocardium, leading to heart failure and death when the extent of injury is severe.Achieving cardiac regeneration or stimulating endogenous repair mechanisms to restore cardiac function after injury has been a goal of countless investigators. In the last decade scientists have questioned whether the mature heart truly l......
-
Cancer vaccines From theory to practice, ushering in a new era of cancer prevention
When one hears the word “vaccine,” many people think of vaccines against infectious agents, such as viruses and bacteria.The idea of vaccination against cancer has a long history and was initially built on the observation that some tumors spontaneously regress in patients experiencing an acute infection. How a non-specific innate immune response against bacterial products could translate into a specific anti-tumor immune response was explained subsequently by the discovery that dendritic cells (DCs) could acquire immunogenic tumor-derived peptides released during the innate immune response. This led to the hypothesis that use of tumor-derived antigens, if delivered to the immune sy......
-
Breakthrough in the Treatment of Burn Wounds: New Strategies Helping Rapid Healing
Burn trauma is an injury that can be caused by heat, electricity, chemical or radiation. Depending on the area affected and the depth of the burn, burn patients can experience a large number of potentially fatal complications, including shock, infection, electrolyte imbalances, and multiple organ failure. Unlike acute wound healing, tendon repair, and intimal healing, the large amount of exudate in burn wounds often leads to persistent inflammation, a high risk of infection, and tissue edema, resulting in a prolonged healing process. Burn patients who have infections are twice as likely to die as those who do not, because an immune system disorder increases a patient's risk of infe......