Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma ( RCC ). Tumor‐infiltrating immune cells ( TIIC s) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIIC s in RCC and further reveal the independent prognostic values of TIIC s. CIBERSORT , an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIIC s and immune checkpoint modulators with overall survival ( OS ). We found that CD 8+ T cells were associated with prolonged OS (hazard ratio [ HR ] = 0.09, 95% confidence interval [ CI ].01‐.53; P = 0.03) in chromophobe carcinoma ( KICH ). A higher proportion of regulatory T cells was associated with a worse outcome ( HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma ( KIRC ). In renal papillary cell carcinoma ( KIRP ), M1 macrophages were associated with a favorable outcome ( HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome ( HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA 4 and LAG 3 were associated with a poor prognosis in KIRC , and IDO 1 and PD ‐L2 were associated with a poor prognosis in KIRP . This study indicates TIIC s are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.

Dendritic cells (DCs) are potent and specialized antigen presenting cells, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses against cancer. Tumor cells can escape from immune attack by secreting suppressive cytokines that solely or cooperatively impair the immune function of DCs. However, the underlying mechanisms are not fully defined. Vascular endothelial growth factor (VEGF) has been identified as a major cytokine in the tumor microenvironment. To elucidate the effects of VEGF on the motility and immune function of mature DCs (mDCs), the cells were treated with 50 ng/mL VEGF and investigated by proteomics and molecular biological technologies. The results showed that VEGF can impair the migration capacity and immune function of mDCs through the RhoA‐cofilin1 pathway mediated by the VEGF receptor 2, suggesting impaired motility of mDCs by VEGF is one of the aspects of immune escape mechanisms of tumors. It is clinically important to understand the biological behavior of DCs and the immune escape mechanisms of tumor as well as how to improve the efficiency of antitumor therapy based on DCs.

Alternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. There are no reliable features to predict survival outcomes for ovarian cancer patients. In this study, comprehensive profiling of AS events was conducted by integrating AS data and clinical information of ovarian serous cystadenocarcinoma (OV). Survival-related AS events were identified by Univariate Cox regression analysis. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to construct the prognostic signatures within each AS type. Furthermore, we established a splicing-related network to reveal the potential regulatory mechanisms between splicing factors and candidate AS events. A total of 730 AS events were identified as survival-associated splicing events, and the final prognostic signature based on all seven types of AS events could serve as an independent prognostic indicator and had powerful efficiency in distinguishing patient outcomes. In addition, survival-related AS events might be involved in tumor-related pathways including base excision repair and pyrimidine metabolism pathways, and some splicing factors might be correlated with prognosis-related AS events, including SPEN, SF3B5, RNPC3, LUC7L3, SRSF11 and PRPF38B. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development.

The aim of this study is to explore the effect of exhaustive exercise on erythrocyte band 3 (SLC4A1; EB3). The association between the alterations of EB3 and red blood cell (RBC) deformability induced by exercise-induced dysfunction has been investigated. Rats were divided among 2 groups: (i) control (C), and (ii) exercise exhausted (E). RBC deformability was investigated in the rats in the exhaustive exercise and control groups. Erythrocytes from the control and exercise-exhausted groups were evaluated for the expression of erythrocyte band 3 through immunoblotting and immunofluorescence studies. Exhaustive exercise led to significant increments in the levels of clustering of erythrocyte band 3 along with the conjugation of membrane proteins to form high-molecular-weight complexes (P < 0.05). Under shear stresses, RBC deformability was found to decline significantly in the exhaustive exercise groups compared with the control group. These data suggest that the RBC dysfunction observed during exercise-induced oxidative stress could be associated with alterations in the structure and function of erythrocyte band 3, which in turn leads to dysfunction in the rheological properties of RBCs. These results provide further insight into erythrocyte damage induced by exhaustive exercise.

Background/Aims: In vitro studies have shown that band-3 function is mainly regulated by its phosphorylation status. The main purpose of the study was to investigate whether band-3 phosphorylation status interferes with an exhaustive running exercise-related dysfunction of RBC deformability. Methods: Rats were divided into sedentary control (C) and exercise test (ET) groups. The ET group was divided further into exhaustive running exercise (ERE) and moderate running exercise (MRE) subgroups. Results: Tyrosine phosphorylation of band-3 was significantly elevated in the absence of reducing agent, consistent with the emergence of band-3 clustering in the ERE group compared with the control and MRE groups. The elongation index (EI) was found to decline significantly in the ERE group compared with the C and MRE groups under shear stress (control group, 0.41 ± 0.01 at 3 Pa and 0.571 ± 0.008 at 30 Pa; ERE group, 0.3140 ± 0.013 at 3 Pa and 0.534 ± 0.009 at 30 Pa; P < 0.001 and P < 0.002, respectively). Conclusion: Our results suggest that exhaustive running exercise results in elevated band-3 tyrosine phosphorylation and alters band-3 membrane organization. Furthermore, it appears that exhaustive running exercise induced band 3 phosphorylation is due to the oxidation of critical sulfydryl groups of a membrane phosphatase (PTP).