Immunity
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Inhibition of immune regulatory checkpoints, such as CTLA-4 and the PD-1-PD-L1 axis, is at the forefront of immunotherapy for cancers of various histological types. However, such immunotherapies fail to control neoplasia in a significant proportion of patients. Here, we review how a range of cancer-cell-autonomous cues, tumor-microenvironmental factors, and host-related influences might account for the heterogeneous responses and failures often encountered during therapies using immune-checkpoint blockade. Furthermore, we describe the emerging evidence of how the strong interrelationship between the immune system and the host microbiota can determine responses to cancer therapies, and we introduce a concept by which prior or concomitant modulation of the gut microbiome could optimize therapeutic outcomes upon immune-checkpoint blockade.
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Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of morbidity and mortality worldwide. Current immunological mechanisms do not explain the basis of cellular dysfunction and organ failure, the ultimate cause of death. Here we review current dogma and argue that it is time to delineate novel immunometabolic and neurophysiological mechanisms underlying the altered cellular bioenergetics and failure of epithelial and endothelial barriers that produce organ dysfunction and death. These mechanisms might hold the key to future therapeutic strategies.
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A major function of a subfamily of NLR (nucleotide-binding domain, leucine-rich repeat containing, or NOD-like receptor) proteins is in inflammasome activation, which has been implicated in a multitude of disease models and human diseases. This work will highlight key progress in understanding the mechanisms that activate the best-studied NLRs (NLRP3, NLRC4, NAIP, and NLRP1) and in uncovering inflammasome NLRs.
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Dendritic cells (DCs) initiate and maintain adaptive T helper 2 (Th2) cell responses to inhaled allergens in asthma. Various functions like antigen uptake, migration to the draining LNs, and induction of tolerance and adaptive immunity are not equally shared by all subsets of DCs, adding considerable complexity to understanding the immunology of allergic sensitization. ⋯ Clinically relevant allergens, as well as environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells, basophils, and DCs. This review summarizes the recent progress on our understanding how DCs control Th2 cell immunity in the lung.