Expression of PD-1 mitigates phagocytic activities TAM in osteosarcoma.

The high expression of programmed death 1 (PD-1) is a hallmark of T cell exhaustion, consequently inhibiting the anti-tumor immunity, tumor-associated macrophages (TAMs) aggravate Osteosarcoma (OS) progression. However, PD-1 expression on TAMs in OS metastasis remains unclear. Here, we used scRNA-Seq of 15500 individual cells from human OS lung metastatic lesion, identified thirteen major cell clusters. Our data revealed that tumor-infiltrating lymphocytes (TILs) OS lung metastatic accompanied by accumulation of exhausted T cells and regulatory T cells (Tregs). CD3+ T cells from human OS lung metastatic exhibited lower proliferation than in primary tissue. Importantly, TAMs mainly comprise immunosuppressive M2 phenotype in OS metastasis. Mechanistically, we found that PD-1 of TAMs inhibits the phagocytic potency, further promoting the progression of OS metastasis. Therefore, the study provides a strong technical support for OS immunotherapy based on PD-1 inhibitors.

Morphological and molecular characteristics of Sarcocystis bertrami from horses and donkeys in China.

While Sarcocystis parasites from the muscles of donkey and horse have been characterized as different species, similarities between the parasites in these host raises questions about this assignment (Levine and Tadros, 1980; Matuschka, 1983; Odening et al., 1995b). To resolve this, we examined the tissue cysts of Sarcocystis collected from donkeys and horses were studied by morphological and molecular methods. Morphological studies performed by light microscopy (LM) revealed that each of two types of cysts were present in samples from each host type. Under LM, villar protrusions (VP) were sometimes observed on the larger (Type I) and smaller (Type II) of these cyst types; when present, these were sometimes short and sometimes long. By electron microscopy (EM), VPs from both horse and donkey cysts were found to share similar structures, appearing to be typical of 'type 11a' VPs found on the Sarcocystis wall of Sarcocystis fayeri as described by Dubey et al., 1977. The VP of cysts in both horses and donkeys contained microtubules extending from the villar tips to the ground substance (GS). Ovoid, osmiophilic bodies (OB) were found along the length of the microtubules within the villi, but this feature was not found in all VP. To understand the phylogeny of the parasites, a portion of the coxI gene was sequenced from 22 isolated cysts (9 from donkeys and 13 from horses). Phylogenetic relationships were reconstructed from these sequences and the closest homologues available in GenBank, revealing that all of the samples, regardless of host origin or morphological appearance under LM, grouped in one clade. Ours is the first attempt to combine morphological measurements with coxI sequences in assessing such equine parasites; the results confirm a close relationship of the parasites from horse and donkey with S. fayeri. Further, the data suggest that the cysts in each host likely belong to the same species. As the first named species was Sarcocystis bertrami, we propose S. bertrami (syn. Sarcocystis fayeri) as the descriptor for this parasite of both horses and donkeys. Ultimately, this finding will only be validated by cross-transmission infection experiments that score the ability of parasite isolates from one Equus to infect the other.

Th17/Treg imbalance is an indicator of liver cirrhosis process and a risk factor for HCC occurrence in HBV patients.

OBJECTIVE: To determine the impact of T helper 17 cell (Th17)/regulatory T cell (Treg) ratio imbalance on the process and prognosis of hepatitis B virus (HBV)-related liver cirrhosis. METHODS: Patients with HBV who refused to accept any therapy from were recruited from 2009 to 2014 and followed-up to August 2016. Based on a liver stiffness measurement (LSM), the patients were divided into a low LSM group and a high LSM group. After propensity score matching, 150 patients were included. The peripheral blood of all subjects was tested using a flow cytometer to measure the Th17 and Treg cell frequencies and the Th17/Treg ratio. Spearman rank correlation, log-rank test, Cox regression model, and receiver operating characteristic (ROC) curves were applied to analyze the correlation between the Th17/Treg ratio and LSM level and the risk factors of HCC occurrence and to predict the Th17/Treg ratio for the LSM level. RESULTS: Th17 and Treg cell frequencies and the Th17/Treg ratio were significantly different between the low and high LSM groups. The Th17/Treg ratio showed a strong positive association with LSM level (r=0.631, P<0.01). Furthermore, the Th17/Treg ratio was an independent factor influencing the HCC occurrence, which was tested using a Cox regression model. The area under the ROC curve of the Th17/Treg ratio for predicting LSM level was 0.783 (95% CI 0.705-0.861). CONCLUSION: Th17/Treg ratio imbalance is an indicator of the liver cirrhosis process and a risk factor for HCC occurrence in patients infected with HBV.