BackgroundRegulatory T (Treg) cells have an immunosuppressive function in cancer, but the underlying mechanism of immunosuppression in the tumor microenvironment (TME) is unclear.MethodsWe compared the phenotypes of T cell subsets, including Treg cells, obtained from peripheral blood, malignant effusion, and tumors of 103 cancer patients. Our primary focus was on the expression of immune checkpoint (IC)-molecules, such as programmed death (PD)-1, T-cell immunoglobulin and mucin-domain containing (TIM)-3, T cell Ig and ITIM domain (TIGIT), and cytotoxic T lymphocyte antigen (CTLA)-4, on Treg cells in paired lymphocytes from blood, peritumoral tissue, and tumors of 12 patients with lung cancer. To identify the immunosuppressive mechanisms acting on tumor-infiltrating Treg cells, we conducted immunosuppressive functional assays in a mouse model.ResultsCD8+, CD4+ T cells, and Treg cells exhibited a gradual upregulation of IC-molecules the closer they were to the tumor. Interestingly, PD-1 expression was more prominent in Treg cells than in conventional T (Tconv) cells. In lung cancer patients, higher levels of IC-molecules were expressed on Treg cells than on Tconv cells, and Treg cells were also more enriched in the tumor than in the peri-tumor and blood. In a mouse lung cancer model, IC-molecules were also preferentially upregulated on Treg cells, compared to Tconv cells. PD-1 showed the greatest increase on most cell types, especially Treg cells, and this increase occurred gradually over time after the cells entered the TME. PD-1 high-expressing tumor-infiltrating Treg cells displayed potent suppressive activity, which could be partially inhibited with a blocking anti-PD-1 antibody.ConclusionsWe demonstrate that the TME confers a suppressive function on Treg cells by upregulating IC-molecule expression. Targeting IC-molecules, including PD-1, on Treg cells may be effective for cancer treatment.

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The equilibrium phase of cesium lead iodide (CsPbI3) at room temperature is yellow and optically inactive due to its indirect band gap. The metastable black phase of CsPbI3 on the other hand exhibits optical properties that are suitable for photovoltaic and light-emitting devices. Here, we examine the stability of the black phase of ligand-stabilized CsPbI3 nanocrystals heated in humid air. Water vapor is known to catalyze the transition of CsPbI3 from the black phase to the yellow phase. Uniform nanocrystals with cube shape were synthesized with capping ligand mixtures of oleylamine and oleic acid or diisooctylphosphinic acid, assembled into superlattices with preferred crystal orientation, and studied using grazing incidence small- and wide-angle X-ray scattering with in situ heating. The black-phase nanocrystals are found to inhabit the γ-orthorhombic phase and do not revert to the equilibrium yellow δ-orthorhombic phase until reaching a relatively high temperature, between 170 and 200 °C, coinciding with superlattice degradation.

C-C receptor 7 (CCR7) is important to allow T cells and dendritic cells to migrate toward CCL19- and CCL21-producing cells in the T-cell zone of the spleen and lymph nodes. The role of this chemokine receptor in regulating the homeostasis of effector and memory T cells during acute viral infection is poorly defined, however. In this study, we show that CCR7 expression alters memory CD8 T-cell homeostasis following lymphocytic choriomeningitis virus infection. Greater numbers of CCR7-deficient memory T cells were formed and maintained compared with CCR7-sufficient memory T cells, especially in the lung and bone marrow. The CCR7-deficient memory T cells also displayed enhanced rates of homeostatic turnover, which may stem from increased exposure to IL-15 as a consequence of reduced exposure to IL-7, because removal of IL-15, but not of IL-7, normalized the numbers of CCR7-sufficient and CCR7-deficient memory CD8 T cells. This result suggests that IL-15 is the predominant cytokine supporting augmentation of the CCR7−/− memory CD8 T-cell pool. Taken together, these data suggest that CCR7 biases memory CD8 T cells toward IL-7–dependent niches over IL-15–dependent niches, which provides insight into the homeostatic regulation of different memory T-cell subsets.

Summary The present study investigated the clinical usefulness of plasma real‐time polymerase chain reaction (PCR) (plasma‐PCR) in the prevention of BK virus‐associated nephropathy (BKVAN). First, we investigated the diagnostic value of plasma BK‐PCR, urine BK‐PCR, and urine cytology for the prediction of BKVAN retrospectively. Then we designed a prospective study of regular plasma‐PCR monitoring and pre‐emptive immunosuppression (IS) reduction based on the result. In the retrospective cohort, the prevalence of BKVAN was 3.7% (14/379) and the positive rate of decoy cells, urine‐PCR (>1 × 1010 copies/ml), and plasma‐PCR (>1 × 104 copies/ml) was 18.6%, 11.1%, and 5.5%, respectively. Plasma‐PCR was superior to urine‐PCR or urine cytology in specificity and positive predictive value for detection of BKVAN. In prospective study, regular monitoring of plasma‐PCR detected significant BKV viremia in 8.3% (12/145) and BKVAN in 1 patient (0.6%). After IS reduction, BKV viremia was eliminated in 91.6% (11/12) within 103 days (25–254). In patients with viremia, the frequency of acute rejection did not increase and allograft function did not differ significantly compared with those in patients without viremia during the first year post‐transplant (P > 0.05, in both). Plasma‐PCR is useful to predict an increased risk for BKVAN, and regular monitoring is effective to prevent the development of BKVAN.