Frontiers in immunology
-
Frontiers in immunology · Jan 2018
ReviewInnate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy.
Clinical and technological advances promoting early hemorrhage control and physiologic resuscitation as well as early diagnosis and optimal treatment of sepsis have significantly decreased in-hospital mortality for many critically ill patient populations. However, a substantial proportion of severe trauma and sepsis survivors will develop protracted organ dysfunction termed chronic critical illness (CCI), defined as ≥14 days requiring intensive care unit (ICU) resources with ongoing organ dysfunction. A subset of CCI patients will develop the persistent inflammation, immunosuppression, and catabolism syndrome (PICS), and these individuals are predisposed to a poor quality of life and indolent death. ⋯ In addition, we characterize pathogen recognition, the interface between innate and adaptive immune systems, and therapeutic approaches including immune modulators, gut microbiota support, and nutritional and exercise therapy. Finally, we discuss the future of diagnostic and prognostic approaches guided by machine and deep-learning models trained and validated on big data to identify patients for whom these approaches will yield the greatest benefits. A deeper understanding of the pathophysiology of CCI and PICS and continued investigation into novel therapies harbor the potential to improve the current dismal long-term outcomes for critically ill post-injury and post-infection patients.
-
Frontiers in immunology · Jan 2018
ReviewThe Evolving Landscape of Immunotherapy-Based Combinations for Frontline Treatment of Advanced Renal Cell Carcinoma.
Insights into the biology of advanced renal cell carcinoma (aRCC) and the development of agents targeting the vascular endothelial growth factor (VEGF) pathway have positively impacted the outcomes for patients with aRCC. With the recent approval of the dual immune checkpoint inhibitors (ICIs), nivolumab and ipilimumab, by the U. ⋯ The frontline treatment options for renal cell carcinoma are evolving rapidly and will lead to the approval of other combination immunotherapies-especially those with VEGF inhibitors. Here we review the clinical data for dual immune checkpoint inhibition with nivolumab plus ipilimumab as well as the emerging data for ICI plus VEGF inhibitor combinations and discuss the challenges these will pose for the clinical practitioner.
-
Frontiers in immunology · Jan 2018
ReviewImmunological Tolerance and Function: Associations Between Intestinal Bacteria, Probiotics, Prebiotics, and Phages.
Post-birth there is a bacterial assault on all mucosal surfaces. The intestinal microbiome is an important participant in health and disease. The pattern of composition and concentration of the intestinal microbiome varies greatly. ⋯ Hence bacteriophage local control of inflammation and immune responses may be an additional immunological defense mechanism that exploits bacteriophage-mucin glycoprotein interactions that controls bacterial diversity and abundance in the mucin layers of the gut. Moreover, and importantly the efficacy of probiotics may be dependent on the symbiotic incorporation of prebiotics, and the abundance and diversity of the intestinal microbiome encountered. The virome may be an important factor that determines the efficacy of some probiotic formulations.
-
Frontiers in immunology · Jan 2018
ReviewConcepts Collide: Genomic, Immune, and Microbial Influences on the Tumor Microenvironment and Response to Cancer Therapy.
Cancer research has seen unprecedented advances over the past several years, with tremendous insights gained into mechanisms of response and resistance to cancer therapy. Central to this has been our understanding of crosstalk between the tumor and the microenvironment, with the recognition that complex interactions exist between tumor cells, stromal cells, overall host immunity, and the environment surrounding the host. This is perhaps best exemplified in cancer immunotherapy, where numerous studies across cancer types have illuminated our understanding of the genomic and immune factors that shape responses to therapy. ⋯ The gut microbiome plays a central role, with recent evidence revealing that the gut microbiome influences the overall immune set-point, through diverse effects on local and systemic inflammatory processes. Indeed, quantifiable differences in the gut microbiome have been associated with disease and treatment outcomes in patients and pre-clinical models, though precise mechanisms of microbiome-immune interactions are yet to be elucidated. Complexities are discussed herein, with a discussion of each of these variables as they relate to treatment response.
-
Frontiers in immunology · Jan 2018
ReviewBlood Transfusion Management for Patients Treated With Anti-CD38 Monoclonal Antibodies.
Daratumumab has proven to be highly efficacious for relapsed and refractory multiple myeloma (MM) and has recently been approved in the frontline setting for MM patients ineligible for transplantation. In the future, expanded indications are possible for daratumumab and other anti-CD38 monoclonal antibodies in development. ⋯ Given the anticipated increase in utilization of anti-CD38 monoclonal antibodies, as well as the transfusion needs of MM patients, it is critical to understand the nature of this interference with blood bank testing and to optimize clinical and laboratory procedures. In this review, we summarize the pathophysiology of this phenomenon, examine the clinical data reported to date, describe currently available methods to resolve this issue, and lastly provide a guide to clinical management of blood transfusions for patients receiving anti-CD38 monoclonal antibodies.