The pathogenesis of hepatocellular carcinoma (HCC) strongly relates to inflammation, with chronic up‐regulation of pro‐inflammatory mediators standing as a potential unifying mechanism that underscores the origin and progression of HCC independent of aetiology. Activation of the diverse pro‐inflammatory mediators either within the tumour or its microenvironment is part of an active cross‐talk between the progressive HCC and the host, which is known to influence clinical outcomes including recurrence after radical treatments and long‐term survival. A number of clinical biomarkers to measure the severity of cancer‐related inflammation are now available, most of which emerge from routine blood parameters including neutrophil, lymphocyte, platelet counts, as well as albuminaemia and C‐reactive protein levels. In this review, we summarise the body of evidence supporting the biologic qualification of inflammation‐based scores in HCC and review their potential in facilitating the prognostic assessment and treatment allocation in the individual patient. We also discuss the evidence to suggest modulation of tumour‐promoting inflammation may act as a source of novel therapeutic strategies in liver cancer.

Patients suffering from systemic autoimmune diseases are at significant risk of cardiovascular complications. This can be due to systemically increased levels of inflammation leading to accelerated atherosclerosis, or due to direct damage to the tissues and cells of the heart. Cardiac complications include an increased risk of myocardial infarction, myocarditis and dilated cardiomyopathy, valve disease, endothelial dysfunction, excessive fibrosis, and bona fide autoimmune-mediated tissue damage by autoantibodies or auto-reactive cells. There is, however, still a considerable need to better understand how to diagnose and treat cardiac complications in autoimmune patients. A range of inducible and spontaneous mouse models of systemic autoimmune diseases is available for mechanistic and therapeutic studies. For this Review, we systematically collated information on the cardiac phenotype in the most common inducible, spontaneous and engineered mouse models of systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis. We also highlight selected lesser-known models of interest to provide researchers with a decision framework to choose the most suitable model for their study of heart involvement in systemic autoimmunity.

Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Despite ALDH being a poor prognostic factor, the non‐invasive assessment of ALDH activity in vivo has not been possible due to a lack of sensitive and translational imaging agents. Presented in this report are the synthesis and biological evaluation of ALDH1A1‐selective chemical probes composed of an aromatic aldehyde derived from N , N ‐diethylamino benzaldehyde (DEAB) linked to a fluorinated pyridine ring either via an amide or amine linkage. Of the focused library of compounds evaluated, N ‐ethyl‐6‐(fluoro)‐ N‐ (4‐formylbenzyl)nicotinamide 4 b was found to have excellent affinity and isozyme selectivity for ALDH1A1 in vitro. Following 18 F‐fluorination, [ 18 F] 4 b was taken up by colorectal tumor cells and trapped through the conversion to its 18 F‐labeled carboxylate product under the action of ALDH. In vivo positron emission tomography revealed high uptake of [ 18 F] 4 b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [ 18 F] 4 b , however, was observed in vivo, which may limit the tissue penetration of this first‐in‐class radiotracer.

Immunotherapy is widely regarded to have the ability to transform the treatment of cancer, with immune checkpoint inhibitors already in use for cancers such as advanced melanoma and non-small cell lung cancer (NSCLC). However, despite its potential, the widespread adoption of immunotherapy for the treatment of other cancers has been largely limited. This can be partly attributed to additional immunosuppressive mechanisms in the tumor microenvironment that help promote and maintain a state of T cell exhaustion. As such, the exploration of combinatory immunotherapies is an active area of research and includes the combination of immune checkpoint inhibitors with cytotoxic therapies, cancer vaccines and monoclonal antibodies against other co-inhibitory and co-stimulatory receptors. Strategies are also being employed to improve the homing, extravasation and survival of chimeric antigen receptor (CAR)-T cells in the tumor microenvironment. Furthermore, the development of immunotherapies targeted to one or multiple neoantigens unique to a specific tumor may act to enhance anti-tumor immunity, as well as reduce immune-related adverse events (irAEs). As immunotherapy evolves to become a mainstay treatment for cancer, it is imperative that optimum treatment regimens that maximize efficacy and limit toxicity are developed. Foremost, appropriate biomarkers must be identified to help tailor combinatory immunotherapies to the individual patient and hence pave the way to a new era of personalized medicine.