M2 macrophages in the tumor microenvironment are important drivers of cancer metastasis. Exosomes play a critical role in the crosstalk between different cells by delivering microRNAs or other cargos. Whether exosomes derived from pro-tumorigenic M2 macrophages (M2-Exos) could modulate the metastatic behavior of renal cell carcinoma (RCC) is unclear. This study found that M2-Exos promotes migration and invasion in RCC cells. Inhibiting miR-21-5p in M2-Exos significantly reversed their pro-metastatic effects on RCC cells in vitro and in the avian embryo chorioallantoic membrane in vivo tumor model. We further found that the pro-metastatic mechanism of miR-21-5p in M2-Exos is by targeting PTEN-3′UTR to regulate PTEN/Akt signaling. Taken together, our results demonstrate that M2-Exos carries miR-21-5p promote metastatic features of RCC cells through PTEN/Akt signaling. Reversing this could serve as a novel approach to control RCC metastasis.

Background: COVID-19 has spread widely worldwide, causing millions of deaths. We aim to explore the association of immunological features with COVID-19 severity. Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature. Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of immune cells including CD3⁺ T cell (× 10⁶, MD, − 413.87; 95%CI, − 611.39 to − 216.34), CD4⁺ T cell (× 10⁶, MD, − 203.56; 95%CI, − 277.94 to − 129.18), CD8⁺ T cell (× 10⁶, MD, − 128.88; 95%CI, − 163.97 to − 93.79), B cell (× 10⁶/L; MD, − 23.87; 95%CI, − 43.97 to − 3.78) and NK cell (× 10⁶/L; MD, − 57.12; 95%CI, − 81.18 to − 33.06), and significantly higher levels of cytokines including TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of chemokines as MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant difference was found in other indicators such as Treg cell (× 10⁶, MD, − 0.13; 95%CI, − 1.40 to 1.14), CD4⁺/CD8⁺ ratio (MD, 0.26; 95%CI, − 0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, − 0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, − 0.49 to 0.60), IL-4 (pg/ml; MD, − 0.03; 95%CI, − 0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, − 0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, − 2.88 to 4.75). Conclusion: Our meta-analysis revealed significantly lower levels of immune cells (CD3⁺ T, CD4⁺ T, CD8⁺ T, B and NK cells), higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases in comparison to mild cases of COVID-19. Measurement of immunological features could help assess disease severity for effective triage of COVID-19 patients.

Exosomes are extracellular vesicles that modulate essential physiological and pathological signals. Communication between cancer cells that express the von Hippel-Lindau (VHL) tumor suppressor gene and those that do not is instrumental to distant metastasis in renal cell carcinoma (RCC). In a novel metastasis model, VHL(−) cancer cells are the metastatic driver, while VHL(+) cells receive metastatic signals from VHL(−) cells and undergo aggressive transformation. This study investigates whether exosomes could be mediating metastatic crosstalk. Exosomes isolated from paired VHL(+) and VHL(−) cancer cell lines were assessed for physical, biochemical, and biological characteristics. Compared to the VHL(+) cells, VHL(−) cells produce significantly more exosomes that augment epithelial-to-mesenchymal transition (EMT) and migration of VHL(+) cells. Using a Cre-loxP exosome reporter system, the fluorescent color conversion and migration were correlated with dose-dependent delivery of VHL(−) exosomes. VHL(−) exosomes even induced a complete cascade of distant metastasis when added to VHL(+) tumor xenografts in a duck chorioallantoic membrane (dCAM) model, while VHL(+) exosomes did not. Therefore, this study supports that exosomes from VHL(−) cells could mediate critical cell-to-cell crosstalk to promote metastasis in RCC.

Background: We aim to explore the association of immunological features with COVID-19 severity.Methods: We conducted a meta-analysis to estimate mean difference (MD) of immune cells and cytokines levels with COVID-19 severity in PubMed, Web of Science, Scopus, the Cochrane Library and the grey literature.Results: A total of 21 studies with 2033 COVID-19 patients were included. Compared with mild cases, severe cases showed significantly lower levels of some immune cells, CD3⁺ T cell (×10⁶, MD, -413.87; 95%CI, -611.39 to -216.34), CD4⁺ T cell (×10⁶, MD, -203.56; 95%CI, -277.94 to -129.18), CD8⁺ T cell (×10⁶, MD, -128.88; 95%CI, -163.97 to -93.79), B cell (×10⁶/L; MD, -23.87; 95%CI, -43.97 to -3.78) and NK cell (×10⁶/L; MD, -57.12; 95%CI, -81.18 to -33.06), and significantly higher levels of some cytokines, TNF-α (pg/ml; MD, 0.34; 95%CI, 0.09 to 0.59), IL-5 (pg/ml; MD, 14.2; 95%CI, 3.99 to 24.4), IL-6 (pg/ml; MD, 13.07; 95%CI, 9.80 to 16.35), and IL-10 (pg/ml; MD, 2.04; 95%CI, 1.32 to 2.75), and significantly higher levels of some chemokines, MCP-1 (SMD, 3.41; 95%CI, 2.42 to 4.40), IP-10 (SMD, 2.82; 95%CI, 1.20 to 4.45) and eotaxin (SMD, 1.55; 95%CI, 0.05 to 3.05). However, no significant differences were found in other indicators, Treg cell (×10⁶, MD, -0.13; 95%CI, -1.40 to 1.14), CD4⁺/CD8⁺ ratio (MD, 0.26; 95%CI, -0.02 to 0.55), IFN-γ (pg/ml; MD, 0.26; 95%CI, -0.05 to 0.56), IL-2 (pg/ml; MD, 0.05; 95%CI, -0.49 to 0.60), IL-4 (pg/ml; MD, -0.03; 95%CI, -0.68 to 0.62), GM-CSF (SMD, 0.44; 95%CI, -0.46 to 1.35), and RANTES (SMD, 0.94; 95%CI, -2.88 to 4.75).Conclusion: Our meta-analysis revealed significant lower levels of immune cells (CD3⁺ T, CD4⁺ T, CD8⁺ T, B and NK cells), significant higher levels of cytokines (TNF-α, IL-5, IL-6 and IL-10) and significant higher levels of chemokines (MCP-1, IP-10 and eotaxin) in severe cases compared with mild cases of COVID-19. Measurement of immunological features could help to assess disease severity for effective triage of COVID-19 patients.

Background: Novel coronavirus pneumonia (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread over the globe. The knowledge about SARS-CoV-2 infection in immunocompromised patients was limited. Case presentation: We presented here two human immunodeficiency virus (HIV)-infected cases with laboratory confirmed COVID-19 and clinically confirmed COVID-19, respectively. The patients both presented with fever at illness onset and patchy shadows in radiological images of lungs. Laboratory findings revealed leukopenia, lymphopenia and positive anti-HIV antibody. The younger case had a moderate course and was discharged after a 28-day hospitalization. However, the elder case with multiple comorbidities developed dyspnea and died on the fourth day after admission. Conclusions: Combining our data with two case reports, we summarize that disease course varies in HIV-infected patients with COVID-19. More attention should be paid to the management of these patients. Whether there is any difference about clinical characteristics and prognosis of COVID-19 between HIV-infected and non-HIV infected patients, remains to be further investigated.