The patients with TNBCs with combined Low-TILs and High-PD-L1 status in pre-PST situation showed unfavorable prognosis. The subset of TNBCs with Low-TILs and High-PD-L1 status could be the therapeutic target for immune checkpoint inhibitor.
Tumor endothelial cells (TEC) lining tumor blood vessels actively contribute to tumor progression and metastasis. In addition to tumor cells, TEC may develop drug resistance during cancer treatment, allowing the tumor cells to survive chemotherapy and metastasize. We previously reported that TECs resist paclitaxel treatment via upregulation of ABCB1. However, whether TEC phenotypes are altered by anticancer drugs remains to be clarified. Here, we show that ABCB1 expression increases after chemotherapy in urothelial carcinoma cases. The ratio of ABCB1-positive TEC before and after first-line chemotherapy in urothelial carcinoma tissues (n ¼ 66) was analyzed by ABCB1 and CD31 immunostaining. In 42 cases (64%), this ratio increased after first-line chemotherapy. Chemotherapy elevated ABCB1 expression in endothelial cells by increasing tumor IL8 secretion. In clinical cases, ABCB1 expression in TEC correlated with IL8 expression in tumor cells after first-line chemotherapy, leading to poor prognosis. In vivo, the ABCB1 inhibitor combined with paclitaxel reduced tumor growth and metastasis compared with paclitaxel alone. Chemotherapy is suggested to cause inflammatory changes in tumors, inducing ABCB1 expression in TEC and conferring drug resistance. Overall, these findings indicate that TEC can survive during chemotherapy and provide a gateway for cancer metastasis. Targeting ABCB1 in TEC represents a novel strategy to overcome cancer drug resistance.Significance: These findings show that inhibition of ABCB1 in tumor endothelial cells may improve clinical outcome, where ABCB1 expression contributes to drug resistance and metastasis following first-line chemotherapy.
The limitation of cytologic still images is one of the reasons why telecytology has not met with widespread acceptance by the cytology community. Cytologic still image only displays a single depth of field, and this is a particularly acute problem in cytology where the specimen is often much thicker than a single microscopic depth of focus. In this article, we examine the validity of a "z-axis" video of a microscopic field of interest.After observing videos of fields of interest from 10 cases, five cytotechnologists reached suitable cytologic findings and diagnosed the fields correctly in great majority of cases. Five other cytotechnologists, who looked only at a single representative still image, could not always make a correct diagnosis. The difference between two observer groups was statistically significant by Wilcoxon's matched pairs signed-rank test.The results indicate that "z-axis" video of microscopic field of interest provides a similar experience to "focusing through" observation of the specimen under a microscope and may improve an accuracy of primary telecytodiagnosis. And we expect that video image telecytology will strongly influence cytology, especially in education and training.
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