Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness and/or bone tropism may have a prognostic potential to identify patients profiting from metastases‐directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n = 24) during radiotherapy with CellSearch, multicolor flow cytometry and imaging cytometry. Analysis of copy‐number alteration indicates a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3%) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4‐expressing subpopulation representing 28.6% of the total CTC population remained stable up to 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem‐like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis‐directed radiotherapy.

Understanding the biological basis of clinical risk factors for severe COVID–19 is required to ensure at–risk patient populations receive appropriate clinical care. Patients with decompensated liver cirrhosis, in particular those classified as Childs–Pugh class B and C, are at increased risk of severe COVID–19 upon infection with SARS–CoV–2. The biological mechanisms underlying this are unknown. We hypothesised this may be due to changes in expression levels of intrinsic antiviral proteins within the serum as well as alterations in the innate immune response to SARS–CoV–2 infection. We identified significant alterations in the serum proteome of patients with more severe liver disease and an increased frequency of auto–antibodies capable of neutralising type I interferons. No difference in SARS–CoV–2 pseudoparticle infection or live SARS–CoV–2 virus infection was observed with serum from decompensated cirrhotic patients. Principal component analysis of the serum proteome identified two main clinical parameters associated with serum proteome changes – aetiology and MELD–Na score. Among patients with MELD-Na scores >20 we detected significant inhibition of IFN–α2b and IFN-α8 signalling but not IFN–β1a, mediated by auto–antibodies. Our results suggest pre–existing neutralising auto–antibodies targeting type I IFN may increase the likelihood of severe COVID–19 in chronic liver disease patients upon SARS–CoV–2 infection and may also be of relevance to other viral infections in this patient population.

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