Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8 T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8 T cells and Tregs and represses the CD8 T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers.

Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer, but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes. To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8 T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.

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Heating the human body to maintain a relatively constant temperature is pivotal for various human functions. However, most of the current heating strategies are energyconsuming and energy-wasting and cannot cope with the complex and changing environment. Developing materials and systems that can heat the human body precisely via an efficient energy-saving approach no matter indoors/outdoors, day/night, and sunny/cloudy is highly anticipated for mitigating the growing energy crisis and global warming but is still a great challenge. Here, we demonstrate the low mid-infrared radiative (mid-IR) emissivity characteristic of Ti 3 C 2 T x MXene and then apply it for energy-free passive radiative heating (PRH) on the human body. Our strategy is realized by simply decorating the cheap nanoporous polyethylene (nanoPE) textile with MXene. Impressively, the as-obtained 12 μm thick MXene/nanoPE textile shows a low mid-IR emissivity of 0.176 at 7−14 μm and outstanding indoor PRH performance on the human body, which enhances by 4.9 °C compared with that of traditional 576 μm thick cotton textile. Meanwhile, the MXene/nanoPE textile exhibits excellent active outdoor solar heating and indoor/outdoor Joule heating capability. The three heating modes integrated in this wearable MXene/nanoPE heating system can be switched easily or combined arbitrarily, making this thin heating system able to heat the human body precisely in various scenarios like indoors/outdoors, day/night, and sunny/ cloudy, providing multiple promising and energy-saving solutions for future all-day personal precision thermal management.

A novel variant of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has recently emerged and rapidly surpassed others in prevalence. This mutation is in linkage disequilibrium with an ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis on wild-type human codon optimized Spike to introduce the D614G variant. Using multiple human cell lines, including human lung epithelial cells, we found that the lentiviral particles pseudotyped with Spike D614G are more effective at transducing cells than ones pseudotyped with wild-type Spike. The increased transduction with Spike D614G ranged from 1.3 to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2, and 1.5 to 7.7-fold in A549ACE2 and Huh7.5ACE2 overexpressing ACE2. Furthermore, trans-complementation of SARS-CoV-2 virus with Spike D614G showed an increased infectivity of human cells. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, we show that the G614 variant is more resistant to proteolytic cleavage in human cells, suggesting a possible mechanism for the increased transduction.