Chronic stress promotes tumor immune evasion via the suppression of MHC-I expression and the upregulation of PD-L1.

Chronic stress induces cancer initiation and progression via regulation of diverse cancer risk factors including immune evasion. Our previous research demonstrated that ß-adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress, but the underlying mechanism of immune escape remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth and tumor escape from T cell surveillance. Chronic restraint stress reduced intratumor MHC-I expression and enhanced PD-L1 expression, whereas propranolol rectified the changes of MHC-I and PD-L1. Under chronic stress, the activated MAPK pathway suppressed MHC-I production by inactivating STAT1/IRF1 signaling pathway, and promoted PD-L1 translation by elevating eIF2α phosphorylation. These findings support the crucial role of ß-adrenergic signaling cascade in the tumor escape from T cell surveillance under chronic restraint stress.

Microstructure, mechanical, corrosion properties and cytotoxicity of beta­calcium polyphosphate reinforced ZK61 magnesium alloy composite by spark plasma sintering.

Magnesium alloy (ZK61) and beta-tricalcium phosphate (ß-TCP) composite ZK61/xß-TCP (x = 0, 5, 10, 15 wt%) are fabricated using spark plasma sintering (SPS). In this study, the microstructure, mechanical properties, degradation behavior in simulated body fluid and cytotoxicity tests of composite were investigated. The results show that when the content of ß-TCP was 5 wt%, which could be evenly distributed on the boundary of ZK61 particles. But agglomeration phenomenon appeared when the content of ß-TCP reached 15 wt%. The hardness and the compressive strength increase with increasing of ß-TCP content, and ZK61/15ß-TCP achieves a maximum Vickers hardness of 94.81 HV0.1 and compressive strength of 402 ±â€¯9 MPa. The immersion tests indicate that corrosion resistance of the composites are better than that of ZK61 matrix, especially ZK61/5ß-TCP. Corrosion products of the composite surface are mainly Mg(OH)2, HA and Ca3(PO4)2. The cytotoxicity tests indicate that composite extracts have no toxicity to L-929 cells. These results suggest that ZK61/xß-TCP composites are promising candidate for degradable implant materials.