Highlights d A distinct B cell subset emerges in tumors after chemotherapy d B cells elicit anti-tumor T cell immunity by ICOSL d Complement signals initiated by immunogenic cell death shape B cell phenotypes d Tumor CD55 expression determines the opposite effects of B cells in tumors

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Leptin and melanocortin signaling control ingestive behavior, energy balance, and substrate utilization, but only leptin signaling defects cause hypothalamic hypogonadism and infertility. Although GnRH neurons do not express leptin receptors, leptin influences GnRH neuron activity via regulation of immediate downstream mediators including the neuropeptides neuropeptide Y and the melanocortin agonist and antagonist, α-MSH, agouti-related peptide, respectively. Here we show that modulation of melanocortin signaling in female db/db mice through ablation of agouti-related peptide, or heterozygosity of melanocortin 4 receptor, restores the timing of pubertal onset, fertility, and lactation. Additionally, melanocortin 4 receptor activation increases action potential firing and induces c-Fos expression in GnRH neurons, providing further evidence that melanocortin signaling influences GnRH neuron activity. These studies thus establish melanocortin signaling as an important component in the leptin-mediated regulation of GnRH neuron activity, initiation of puberty and fertility.

Background. Redox plays an essential role in the pathogeneses and progression of tumors, which could be regulated by long noncoding RNA (lncRNA). We aimed to develop and verify a novel redox-related lncRNA-based prognostic signature for clear cell renal cell carcinoma (ccRCC). Materials and Methods. A total of 530 ccRCC patients from The Cancer Genome Atlas (TCGA) were included in this study. All the samples were randomly split into training and test group at a 1 : 1 ratio. Then, we screened differentially expressed redox-related lncRNAs and constructed a novel prognostic signature from the training group using the least absolute shrinkage and selection operation (LASSO) and COX regression. Next, to verify the accuracy of the signature, we conducted risk and survival analysis, as well as the construction of ROC curve, nomogram, and calibration curves in the training group, test group, and all samples. Finally, the redox gene-redox-related lncRNA interaction network was constructed, and gene set enrichment analysis (GSEA) was performed to investigate the status of redox-related functions between high/low-risk groups. Results. A nine-redox-related lncRNA signature consisted of AC025580.3, COLCA1, AC027601.2, DLEU2, AC004918.3, AP006621.2, AL031670.1, SPINT1-AS1, and LAMA5-AS1 was significantly associated with overall survival in ccRCC patients. The signature proved efficient, and thus, a nomogram was successfully assembled. In addition, the GSEA results demonstrated that two major redox-related functions were enhanced in the high-risk group ccRCC patients. Conclusions. Our findings robustly demonstrate that the nine-redox-related lncRNA signature could serve as an efficient prognostic indicator for ccRCC.