Identification and manipulation of tumor associated macrophages in human cancers

Evading immune destruction and tumor promoting inflammation are important hallmarks in the development of cancer. Macrophages are present in most human tumors and are often associated with bad prognosis. Tumor associated macrophages come in many functional flavors ranging from what is known as classically activated macrophages (M1) associated with acute inflammation and T-cell immunity to immune suppressive macrophages (M2) associated with the promotion of tumor growth. The role of these functionally different myeloid cells is extensively studied in mice tumor models but dissimilarities in markers and receptors make the direct translation to human cancer difficult. This review focuses on recent reports discriminating the type of infiltrating macrophages in human tumors and the environmental cues present that steer their differentiation. Finally, immunotherapeutic approaches to interfere in this process are discussed

Oral glucocorticoid therapy and all-cause and cause-specific mortality in patients with rheumatoid arthritis: a retrospective cohort study

Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death