Pancreatic ductal adenocarcinoma (PDAC) is a devastating metastatic disease for which better therapies are urgently needed. Macrophages enhance metastasis in many cancer types, however, the role of macrophages in PDAC liver metastasis remains poorly understood. Here we found that PDAC liver metastasis critically depends on the early recruitment of granulin secreting inflammatory monocytes to the liver. Mechanistically, we demonstrate that granulin secretion by metastasis associated macrophages (MAMs) activates resident hepatic stellate cells (hStCs) into myofibroblasts that secrete periostin, resulting in a fibrotic microenvironment that sustains metastatic tumour growth. Disruption of MAM recruitment or genetic depletion of granulin reduced hStCs activation and liver metastasis. Interestingly, we found that circulating monocytes and hepatic MAMs in PDAC patients express high levels of granulin. These findings suggest that recruitment of granulin expressing inflammatory monocytes plays a key role in PDAC metastasis and may serve as a potential therapeutic target for PDAC liver metastasis.

Objectives Knowledge about self-perceived health can help us understand the health status and needs among migrants and ethnic minorities in the European Union (EU) which is essential to improve equity and integration. The objective was to examine and compare self-perceived health among migrant and ethnic minority groups in the EU countries. Methods Publications were ascertained by a systematic search of PUBMED and EMBASE. Eligibility of studies was based on the abstracts and the full texts. Additional articles were identified via the references. The final number of studies included was 17. Results Publications were identified in 5 out of the 27 EU countries. In regard to self-perceived health, most migrants and ethnic minority groups appeared to be disadvantaged as compared to the majority population even after controlling for age, gender, and socioeconomic factors. Only limited cross-country comparisons could be carried out, still they revealed a parallel pattern of self-perceived health among similar migrant/ethnic minority groups. Conclusions Policies to improve social and health status, contextual factors, and access to healthcare among migrants and ethnic minorities are essential to reduce ethnic inequalities in health.

Our review illustrates lack of appropriate epidemiological data and diversity in the categorization of migrants between studies, which makes valid cross-country comparisons most challenging. After adjusting for socio-economic factors and health status, the existing studies still show systematic variations in somatic healthcare utilization between migrants and non-migrants.

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Macrophages are one of the most abundant immune cells in the tumour microenvironment of solid tumours and their presence correlates with reduced survival in most cancers. Macrophages are present at all stages of tumour progression and stimulate angiogenesis, tumour cell invasion, and intravasation at the primary site. At the metastatic site, macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways. In addition, macrophages promote the growth of disseminated tumour cells at the metastatic site by organising the formation of a supportive metastatic niche. The development of agents inhibiting the recruitment or the protumorigenic effector functions of macrophages in both the primary tumour and at the metastatic site is a promising strategy to improve cancer survival in the future.