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Daley et al. show that NLRP3 signaling in macrophages drives their immune-suppressive phenotype in the pancreatic tumor microenvironment and potentiates tolerogenic T cell differentiation. Conversely, targeting NLRP3 protects against pancreatic oncogenesis and is associated with immunogenic reprograming within the tumor.

Background and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4+, PD1+, Ly6C+CD44+ phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4+ T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.

Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαβ + CD4-CD8-NK1.1innate αβ T cells (iαβT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαβTs represent ∼10% of T lymphocytes infi ltrating PDA in mice and humans. Intratumoral iαβTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαβTs comprised ∼75% of the total intratumoral IL17 + cells. Moreover, iαβT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαβT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4 + and CD8 + T-cell expansion/activation and tumor protection. Collectively, iαβTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets. SIGNIFICANCE: We found that iαβTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαβTs induce a CCR5-dependent immunogenic tumorassociated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy. See related commentary by Banerjee et al., p. 1164.

This case describes an intraoperative incidental finding and surgical removal of ectopic liver tissue attached to the gallbladder during a standard laparoscopic cholecystectomy for acute cholecystitis. These anomalies are rare, with interesting associations and possible clinically relevant complications. The details of the case, along with a brief literature review of embryology, common ectopic sites, and associations/complications, are presented in this paper. Since laparoscopic cholecystectomy is a very common procedure, it is important to increase vigilance of ectopic liver tissues during surgeries to minimize complications and provide optimal management.