BackgroundSystemic radiation treatments that preferentially irradiate cancer cells over normal tissue, known as targeted radionuclide therapy (TRT), have shown significant potential for treating metastatic prostate cancer. Preclinical studies have demonstrated the ability of external beam radiation therapy (EBRT) to sensitize tumors to T cell checkpoint blockade. Combining TRT approaches with immunotherapy may be more feasible than combining with EBRT to treat widely metastatic disease, however the effects of TRT on the prostate tumor microenvironment alone and in combinfation with checkpoint blockade have not yet been studied.MethodsC57BL/6 mice-bearing TRAMP-C1 tumors and FVB/NJ mice-bearing Myc-CaP tumors were treated with a single intravenous administration of either low-dose or high-dose 90Y-NM600 TRT, and with or without anti-PD-1 therapy. Groups of mice were followed for tumor growth while others were used for tissue collection and immunophenotyping of the tumors via flow cytometry.Results90Y-NM600 TRT was safe at doses that elicited a moderate antitumor response. TRT had multiple effects on the tumor microenvironment including increasing CD8 +T cell infiltration, increasing checkpoint molecule expression on CD8 +T cells, and increasing PD-L1 expression on myeloid cells. However, PD-1 blockade with TRT treatment did not improve antitumor efficacy. Tregs remained functional up to 1 week following TRT, but CD8 +T cells were not, and the suppressive function of Tregs increased when anti-PD-1 was present in in vitro studies. The combination of anti-PD-1 and TRT was only effective in vivo when Tregs were depleted.ConclusionsOur data suggest that the combination of 90Y-NM600 TRT and PD-1 blockade therapy is ineffective in these prostate cancer models due to the activating effect of anti-PD-1 on Tregs. This finding underscores the importance of thorough understanding of the effects of TRT and immunotherapy combinations on the tumor immune microenvironment prior to clinical investigation.
We provide evidence for the causal impact of social status on longevity by exploiting a natural experiment in which subjects undergo a shift in their social status without considerable economic impact. We gather data on 4190 scientists who were either nominated for or successfully elected to the Chinese Academy of Science or of Engineering. Being elected as an academician in China is a boost in social status (vice-ministerial level) with negligible direct economic impact (US$30 monthly before 2009). After correcting for two sources of bias, (1) some potential academicians decease too young to be elected, leading to selection bias in favor of academicians and (2) the endogenous relationship between health and social status, we find that the enhanced social status of becoming an academician leads to approximately 1.2 years longer life. Copyright © 2015 John Wiley & Sons, Ltd.
Industry mean wages in China have exhibited sharply increased dispersion since the early1990s. Researchers have attributed this rising inequality within the industrial wage structure to: (i) increasingly competitive labour markets leading to better matches between worker pay, worker skills and employer demands; or (ii) residual government control in some industrial sectors that has generated high wages through monopoly rent sharing. We argue that the rise in China's industrial wage dispersion is primarily attributable to increasingly competitive labour markets, which have led to greater returns to schooling and to efficient redistribution of workers across major industry groups. We cannot reject the null hypothesis that the level or changes in government monopoly power has had negligible impact on China's rising industrial wage dispersion.
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