The B7H4-PDL1 classifier stratifies immuno-phenotype in cervical cancer

Background It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified. Methods A pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis. Results The pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies. Conclusions Totally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.

Anti-Tumor Efficiency of Perillylalcohol/β-Cyclodextrin Inclusion Complexes in a Sarcoma S180-Induced Mice Model

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with β-cyclodextrin (β-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and β-cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the β-CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the β-cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/β-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/β-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.

Distribution of Cytoskeleton Protein Nestin in Acute Leukemia.

Abstract 4721 Objective Nestin was detected in some tumor cells and nestin expression was positive relative with malignancy of glioma, angioma and melanoma. Nestin maybe was considered as marker of tumor malignancy and cell proliferation. There was no report about nestin expression in acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL). Herein, we describe the clinicopathological and immunohistochemical features of 48 patients with acute leukemia, introducing nestin as an additional marker that identifies these tumors .Meanwhile, Nestin and ki67 antigen expression were done to identify the relation of nestin and cell proliferation in AML, and the correlation between histoscore of nestin expression on leukemic blasts and patients' complete remission rate (CR) and overall survival (OS) was analyzed in AML. Methods Nestin and ki67 antigen expression in a series of 37 AML samples, 11 ALL samples, 2 multiple myeloma samples (MM) and 2 chronically myeloid leukemia samples (CML) were done with immunohistochemistry. Histoscore of nestin expression on leukemic blasts with AML and ALL was done and analyzed with independent t-test. The correlation of histoscore of nestin expression with patients' CR rate in AML was analyzed by the method of chi-square test. Patients' OS analysis was determined by the method of Kaplan and Meier, with log-rank analysis to estimate statistical significance in AML. P values of <0.05 were considered significant. Results Among 37 cases with AML, Nestin expression was observed in most leukemic blasts, and matural granulocytic cell also expressed nestin in 30 cases .The ratio of tumor cell expressing nestin and total tumor cells was over fifty percents in AML in 14 patients. The ratio of tumor cell expressing nestin and total tumor cells was over ten percents in AML in 7 patients. The ratio of tumor cell expressing nestin and total tumor cells was less ten percents in AML in 9 patients. Nestin expression was not observed in 8 patients. Where ki67 expressed in AML, nestin expressed intensely in 7 cases with AML. But other cases did not express ki67. However, histoscore of nestin expression on leukemic blasts in AML was not correlated with patients' CR (p=0.701) and OS (p=0.245). Nestin immune-reactivity in ALL mainly focused on matural granulocytic cells, matural lymphocytic cells and tumor cells did not express nestin. Compared with AML, there was significant statistical significance (p=0.007). Conclusions These findings constitute the first conclusive evidence that stem cell marker nestin expression in leukemic blasts with AML, CML, MM, but nestin did not express in leukemic blasts with ALL. Nestin may be a useful immunohistochemical marker for identifying AML and ALL. Nestin expression was not correlated with cell proliferation, patients' CR and OS in AML. Disclosures: No relevant conflicts of interest to declare.