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Tuesday, October 04, 2022 6:03:05 AM
In a series of experiments, it was found that protection against both Chronic Obstructive Pulmonary Disease (COPD) and Acute Respiratory Distress Syndrome (ARDS) could be transferred to naïve mice by dendritic cells expressing the molecule CD103.
CD103 expression by DCs: a new player in lung cancer immunity.
https://www.jimmunol.org/content/200/1_Supplement/56.21
J Immunol May 1, 2018
Abstract
Despite the use of various therapies, lung cancer remains one of the world’s leading causes of death. Cancer immunotherapy is a promising therapeutic avenue, however, molecular and cellular mechanisms involved in cancer immunity remain elusive. Dendritic cells (DCs), which play an important role in CD8+ T cell activation in cancer immunity, can be divided into two major populations, namely DC1 and DC2, and respectively identified by XCR1/CD103 and Sirpa/CD11b expression. Importantly, studies have demonstrated that DC1s promote cancer immune responses. Furthermore, CD103+ DC1s specialize in the transport of tumor antigens to draining lymph nodes and cross-presentation. However, the influence of the cancer environment, where inflammatory factors (such as TNF) and various inflammatory cells are found, on CD103 expression by DC has never been studied. To verify whether lung cancer-induced inflammation modulates CD103 DC population, fresh lung and splenic DCs were isolated in wild type (WT) mice and exposed to GM-CSF (a known inducer of CD103 expression in the lung) with or without TNF. Furthermore, to directly assess the impact of lung cancer on CD103 DC expression, WT mice were euthanized 2 and 3 weeks following intravenous injection of Lewis lung carcinoma (LLC) cells and the percentage of CD103+DC1 was analyzed in lungs. Exposure to TNF blocked the GM-CSF-induced CD103 expression by DCs, independently of the timing at which TNF is added to cultures (before or after GM-CSF). Also, the % of CD103+ DCs gradually decreased in time following LLC injection. This suggests a new mechanism by which lung cancer negatively impacts the function of immune cells to promote cancer development, and could lead to new therapeutic avenues in cancer immunity.
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