Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer Researchers used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells recognizing a mutation in erbb2 interacting protein expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. [Science] Abstract | Press Release Rad50-CARD9 Interactions Link Cytosolic DNA Sensing to Interleukin-1β Production Scientists defined a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens. [Nat Immunol] Abstract | Press Release Tumor Endothelium FasL Establishes a Selective Immune Barrier Promoting Tolerance in Tumors Researchers found the death mediator Fas ligand (FasL) expression was associated with scarce CD8+ infiltration and a predominance of FoxP3+ T regulatory (Treg) cells. Tumor-derived vascular endothelial growth factor A, interleukin 10 and prostaglandin E2 cooperatively induced FasL expression in endothelial cells, which acquired the ability to kill effector CD8+ T cells but not Treg cells because of higher levels of c-FLIP expression in Treg cells. [Nat Med] Abstract IL-22+CD4+ T Cells Promote Colorectal Cancer Stemness via STAT3 Transcription Factor Activation and Induction of the Methyltransferase DOT1L Investigators detected interleukin-22 (IL-22) in patient colorectal cancer tissues that was produced predominantly by CD4+ T cells. In a mouse model, migration of these cells into the colon cancer microenvironment required the chemokine receptor CCR6 and its ligand CCL20. [Immunity] Abstract | Graphical Abstract | Press Release Downmodulation of Tumor Suppressor p53 by T Cell Receptor Signaling Is Critical for Antigen-Specific CD4+ T Cell Responses Downmodulation of tumor suppressor p53 in response to antigen stimulation was found critical for antigen-specific T cell proliferation, and preventing p53 degradation by inhibiting regulating protein Mdm2 prevented antigen-specific T cell proliferation. [Immunity] Abstract | Graphical Abstract IL-27 and IL-12 Oppose Pro-Inflammatory IL-23 in CD4+ T Cells by Inducing Blimp1 Researchers identified the transcriptional regulator Blimp1 as crucial to induce IL-10 in inflammatory T helper cells. Pre-committed T helper 17 cells responded to IL-27 and IL-12 by upregulating Blimp1 and adopt a Tr1-like phenotype characterized by IL-10 and interferon-γ production. [Nat Commun] Abstract IL-21 Induces IL-22 Production in CD4+ T Cells Scientists showed that interleukin (IL)-21 triggers IL-22, but not IL-17 production by CD4+ T cells. Signal transducer and activator of transcription 3, activated by IL-21, controls the epigenetic status of the il22 promoter and its interaction with the aryl hydrocarbon receptor (AhR). IL-21 and AhR signaling in T cells control IL-22 production and the development of dextran sodium sulfate-induced colitis in innate lymphoid cell-deficient mice. [Nat Commun] Abstract Ubiquitination by SAG Regulates Macrophage Survival/Death and Immune Response during Infection Using in vitro and ex vivo approaches, investigators showed that macrophage survival is synchronized by SAG (sensitive to apoptosis gene), which is a key member of the ubiquitin-proteasome system. [Cell Death Differ] Full Article The Oxysterol Receptor LXRβ Protects against DSS- and TNBS-Induced Colitis in Mice Scientists found inflammatory cytokines and chemokines were increased together with increased infiltration of immune cells in the colon epithelium in Lxr-deficient mice. Activation of oxysterol receptors (LXRs) strongly suppressed expression of inflammatory mediators including TNFα. While LXRα had anti-inflammatory effects in CD11b+ immune cell populations, LXRβ in addition had anti-inflammatory effects in colon epithelial cells. [Mucosal Immunol] Abstract Single-Cell RNA Sequencing Reveals T Helper Cells Synthesizing Steroids De Novo to Contribute to Immune Homeostasis Investigators demonstrate production of the steroid pregnenolone by T helper 2 (Th2) cells in vitro and in vivo in a helminth infection model. Single-cell RNA sequencing and quantitative PCR analysis suggest that pregnenolone synthesis in Th2 cells is related to immunosuppression. [Cell Rep] Full Article | Graphical Abstract | Press Release |