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Ovarian cancer is the most lethal female reproductive system tumour. Despite the great advances in surgery and systemic chemotherapy over the past two decades, almost all patients in stages III and IV relapse and develop resistance to chemotherapy after first-line treatment. Ovarian cancer has an extraordinarily complex immunosuppressive tumour microenvironment in which immune checkpoints negatively regulate T cells activation and weaken antitumour immune responses by delivering immunosuppressive signals. Therefore, inhibition of immune checkpoints can break down the state of immunosuppression. Indeed, Immune checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape of many solid tumours. However, ICIs have yielded modest benefits in ovarian cancer. Therefore, a more comprehensive understanding of the mechanistic basis of the immune checkpoints is needed to improve the efficacy of ICIs in ovarian cancer. In this review, we systematically introduce the mechanisms and expression of immune checkpoints in ovarian cancer. Moreover, this review summarises recent updates regarding ICI monotherapy or combined with other small-molecule-targeted agents in ovarian cancer.
We present a provenance study of core ZK2 from the Huanghe (Yellow River) Delta in order to assess the impacts of climate change on the sediment supplies during the last glacial–interglacial cycle. Facies analysis and sequence stratigraphy methods are used to construct the age model. Sr isotopic compositions of ZK2 range from 0.716389 to 0.723884, with 87Sr/86Sr increased with decreasing grain size. Nd and Pb isotopic compositions display two large major excursions during Marine Oxygen Isotope stages (MIS) 2 and 4, with less radiogenic εNd and lower 208Pb/204Pb, 207Pb/204Pb, and 206Pb/204Pb values during these periods. These excursions have been explained in terms of changes in the mixing proportion of sediments from the Loess Plateau and Ordos Plateau, resulting from East Asian monsoon intensity variations. The weak summer monsoon precipitation resulted in decreased erosion of Loess Plateau during MIS 2, 4 and the middle of MIS 3. Meanwhile, both the intensified East Asian winter monsoon and the southward expansions of Mu Us desert significantly enhanced the eolian sand entering the Huanghe. Therefore, our results highlight the impact of monsoon variability on erosion patterns in the Huanghe basin.
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