Xixi Gu

B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.

<h3>Objectives</h3> B and T cells constitute the majority of infiltrating lymphocytes in the kidney and represent the local perpetrators in lupus nephritis (LN), but the underlying pathogenic mechanisms are not well elucidated. The aim of this study is to explore the kidney-specific adaptive immune landscape in patients with active LN at the single-cell level. <h3>Methods</h3> We performed single-cell RNA/B cell receptor (BCR)/T cell receptor (TCR) sequencing analysis on sorting-purified B and T cells from the kidney and paired peripheral blood of patients with active LN, and the periphery of matched controls. Flow cytometry, Assay for Transposase Accessible-sequencing, multiplexed immunohistochemistry and functional studies were performed to validate the transcriptomic results. <h3>Results</h3> High infiltrations of intrarenal atypical B cells (ABCs) and antibody-secreting cells (ASCs) were identified in the B cell compartment. The single-cell BCR repertoire analysis revealed strong clonal expansion of intrarenal ASCs dominated by <i>IGHG1</i> and <i>IGHG3</i> isotypes, accompanied by lower frequencies of heavy-chain and light-chain somatic mutations, compared with the peripheral ASCs. Notably, a unique expansion of <i>IGHG4-59</i> and clonal overlap between ABCs and ASCs was found in kidney-specific clonotypes. In the T cell compartment, we identified granzyme K (GZMK)⁺ CD8 T cells as the dominant kidney-associated T cells which shared inflammation- and stress-related gene pathways with ABCs. Intrarenal GZMK⁺ CD8 T cells highly expressed <i>IFNG</i> and displayed strong communication with ABCs via the type II interferon (IFN) pathway. Intrarenal GZMK⁺ CD8 T cells and ABCs were largely co-localised within the tertiary lymphoid structure, and GZMK⁺ CD8 T cells potentially contributed to the differentiation of ABCs via IFN-γ and interleukin-21. <h3>Conclusions</h3> Our study revealed a potent extrafollicular B cell response linked with overactivation of GZMK⁺ CD8 T cells in the kidney of patients with LN, which may lead to innovative treatments for LN.

The retracted article is: Zhao H, Zhang HW, Zhang T and Gu XM (2016). Tumor necrosis factor alpha gene -308G>A polymorphism association with the risk of esophageal cancer in a Han Chinese population. Genet. Mol. Res. 15: gmr.15025866. Two major concerns were found in this article. Firstly, it was found to be substantially equal to the article "Tumor necrosis factor-alpha gene -308G > A polymorphism alters the risk of hepatocellular carcinoma in a Han Chinese population" published in the Diagnostic Pathology Diagnostic Pathology (2014) 9: 199, by Feng et al.; licensee BioMed Central. 2014 - DOI: 10.1186/s13000-014-0199-3. Secondly, the authors do not discuss limitations of their approaches in the discussion. The discussion is largely an elaboration of the literature in the introduction part. However, even in that context, the discussion does not appropriately review the literature and there are frequent references to conclusions that are not supported by the cited literature. The GMR editorial staff was alerted and after a thorough investigation, there is strong reason to believe that the peer review process was failure. Also, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). The authors and their institutions were advised of this serious breach of ethics.