The objective of this study was to predict the value of lymphocyte subsets in cancer progression. Peripheral blood was obtained from 327 untreated patients with cancer and 158 healthy volunteers. Levels of lymphocyte subsets were determined by flow cytometry. There were decreased levels of natural killer (NK) cells, CD8 + T cells, and naïve CD4 + /CD4 + T cells in untreated patients with cancer compared to those in healthy controls. Inversely, there were elevated levels of the following T‐cell percentages in cancer patients compared to those in healthy controls: memory CD4 + /CD4 + , CD8 + T cells, HLA‐DR/CD8 + , CD8 + CD38 + /CD8 + , and CD4 + /CD8 + . In addition, there are a decreasing trend in terms of CD4 + T‐cell counts and an increase CD8 + HLA‐DR/CD8 + T‐cell and CD8 + CD38 + /CD8 + T‐cell percentages in the advanced stage. An increasing trend with advanced tumor stage and the percentages of CD8 + HLA‐DR/CD8 + T cells and CD8 + CD38 + /CD8 + T cells was shown in this study. There are a negative correlation for CD4 + T‐cell counts and positive correlation for percentages of CD8 + HLA‐DR/CD8 + T cell and CD8 + CD38 + /CD8 + T cells with the lymph node metastasis. In the presence of distant metastatic spread, we observed higher NK‐cell counts, CD8 + HLA‐DR/CD8 + T‐cell percentages, CD8 + CD38 + /CD8 + T‐cell percentages, as well as lower CD4 + T‐cell counts than those in the absence of distant metastases spread. Abnormal levels of NK cell, CD8 + T cells, memory CD4 + /CD4 + , naïve CD4 + / CD4 + , CD8 + HLA‐DR/CD8 + , CD8 + CD38 + /CD8 + , and CD4 + /CD8 + can be a potential blood biomarkers of cancer development. CD4+ T‐cell counts and percentages of CD8 + HLA‐DR/ CD8 + and CD8 + CD38 + / CD8 + can predict the cancer progression.

Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer, which is the malignant tumor with the highest mortality and morbidity in the world. Herein, ZNF280A, a member of the zinc finger protein family carrying two consecutive Cys2His2 zinc finger domains, was shown by us to act as a tumor driver in LUAD. The immunohistochemical analysis of ZNF280A in LUAD indicated its positive correlation with tumor grade, pathological stage and lymphatic metastasis, and negative relationship with patients’ survival. A loss-of-function study revealed the inhibition of LUAD development by ZNF280A in vitro and in vivo, whereas ZNF280A overexpression induced opposite effects. Statistical analysis of gene expression profiling in LUAD cells with or without ZNF280A knockdown identified EIF3C as a potential downstream of ZNF280A, which possesses similar regulatory effects on phenotypes of LUAD cells with ZNF280A. Moreover, downregulation of EIF3C in ZNF280A-overexpressed cells could attenuate neutralize the ZNF280A-induced promotion of LUAD. In summary, our study demonstrated that ZNF280A may promote the development of LUAD by regulating cell proliferation, apoptosis, cell cycle, and cell migration and probably via interacting EIF3C.

BackgroundProgrammed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors therapy is now a routine scheme in cancers. However, the effect of preexisting autoantibodies on the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients is not well understood.MethodsThe present retrospective cohort study evaluated the safety and efficacy of PD-1/PD-L1 inhibitors in patients with preexisting autoantibodies. Patients who received PD-1/PD-L1 inhibitors in the Department of Medical Oncology, Peking Union Medical College Hospital between November 2017 and August 2021 were reviewed.Results67 (37.9%) of the 177 patients, 27 (20.3%) of the 133 patients, and 16 (11.0%) of 146 patients who received PD-1/PD-L1 inhibitors were positive for ANA, anti-Ro52, and antithyroid antibodies, respectively. Preexisting ANA and anti-Ro52 antibody were not associated with the increased risk of immune-related adverse events (irAEs), while thyroid dysfunction was more frequent in patients with positive antithyroid antibody (75.0% versus 13.8%, p < 0.001). The median progression-free survival (PFS, 13.1 versus 7.0 months, p = 0.015) was significantly longer in the ANA-positive patients, while the median overall survival (OS, 14.5 versus 21.8 months, p = 0.67) did not differ significantly between the ANA-positive and ANA-negative groups. Moreover, the preexisting anti-Ro52 and antithyroid antibodies were not significantly associated with PFS and OS.ConclusionsThe presence of ANA and anti-Ro52 antibody were not associated with a higher risk of irAEs, whereas patients positive for antithyroid antibody should monitor closely immune-related thyroid dysfunction. Preexisting ANA might be a predictor of longer PFS, while anti-Ro52 and antithyroid antibodies had no significant effect on survival outcomes in patients receiving PD-1/PD-L1 inhibitors therapy.

Background Treatment for non-small cell lung cancer (NSCLC) has greatly improved in recent years. However, noninvasive early screening for carcinogenesis and progression unclear. The aim of this study was to explore the predictive value of peripheral blood immune cells in untreated NSCLC patients. Methods We retrospectively enrolled 305 untreated NSCLC patients and 132 healthy participants from February 2016 to August 2019 in Peking Union Medical College Hospital. Immune cell levels were determined by flow cytometry and routine blood tests. Results NSCLC patients had lower levels of T lymphocytes, NK cells, CD8+ T cells, naïve CD4+/CD4+, naïve CD4+ T cells and higher levels of CD4+ T cells, memory CD4+/CD4+ T cells, memory CD4+ T cells, CD4+CD28+/CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+/CD8+ T cells, CD8+HLA-DR+/CD8+ T cells, CD8+HLA-DR+ T cells T cells, CD8+CD38+/CD8+ T cells, CD8+CD38+ T cells and CD4+/CD8+ T cells than those in controls. The percentages of specific lymphocyte subtypes were significantly different in cancer patients versus healthy individuals. For instance, cancer patients had lower levels of B cells, CD4+ T cells, naïve CD4+/CD4+ T cells, naïve CD4+ T cells, CD4+CD28+ T cells, CD8+CD28+ T cells and higher levels of NK cells, white blood cells (WBC), monocytes, neutrophils, eosinophils, basophils, monocytes to lymphocyte ratio (MLR), neutrophils to lymphocyte ratio (NLR), eosinophil to lymphocyte ratio (ELR), basophil to lymphocyte ratio (BLR), and blood platelet to lymphocyte ratio (PLR). Conclusions Abnormal T cell levels can be used as an independent predictive biomarker for noninvasive early screening in NSCLC occurrence and progression.

Conductive metal–organic frameworks (MOFs) have recently been applied in electroactive ionic actuators due to their high surface areas and fast ion migration. However, their actuation performance needs to be promoted in terms of high conversion efficiency and large strain. Here, a soft ionic actuator is assembled by designing a hierarchical Cu‐MOFs‐based active material, which is composed of conductive Cu‐catecholate (Cu‐CAT) nanosheets covalently bridged by carboxylic multiwall carbon nanotubes (Cu‐CAT@MWCNT). Benefited from the large electromechanical deformation and rapid response rate of the Cu‐CAT@MWCNT electrodes, the assembled soft actuator exhibits large displacement of 16.6 mm with high bending strain of 0.52% (AC of ±3 V) and a high energy conversion efficiency (3.02%) with cycling stability over 10 000 cycles (in frequency range of 0.1–10 Hz). In addition, it demonstrates the capacity of gripping objects when assembled on a robot. The Cu‐CAT@MWCNT hybrid material‐based electrode points out a feasible pathway to construct soft actuators with improved performance and broadens their applications.

Background: Accumulating evidence has suggested that the extracellular matrix (ECM) plays a vital role in the development and progression of cancer, and could be recognized as a biomarker of the response to immunotherapy. However, the effect of the ECM signature in hepatocellular carcinoma (HCC) is not well understood.Methods: HCC patients derived from the TCGA-LIHC dataset were clustered according to the ECM signature. The differences in prognosis, functional enrichment, immune infiltration, and mutation characteristics between distinct molecular clusters were examined, and its predictive value on the sensitivities to chemotherapy and immunotherapy was further analyzed. Then, a prognostic model was built based on the ECM-related gene expression pattern.Results: HCC patients were assigned into two molecular subtypes. Approximately 80% of HCC patients were classified into cluster A with poor prognosis, more frequent TP53 mutation, and lower response rate to immunotherapy. In contrast, patients in cluster B had better survival outcomes and higher infiltration levels of dendritic cells, macrophages, and regulatory T cells. The prognostic risk score model based on the expression profiles of six ECM-related genes (SPP1, ADAMTS5, MMP1, BSG, LAMA2, and CDH1) demonstrated a significant association with higher histologic grade and advanced TNM stage. Moreover, the prognostic risk score showed good performance in both the training dataset and validation dataset, as well as improved prognostic capacity compared with TNM stage.Conclusions: We characterized two HCC subtypes with distinct clinical outcomes, immune infiltration, and mutation characteristics. A novel prognostic model based on the ECM signature was further developed, which may contribute to individualized prognostic prediction and aid in clinical decision-making.

Background. Lepidic adenocarcinoma (LPA) is an infrequent subtype of invasive pulmonary adenocarcinoma (ADC). However, the clinicopathological features and prognostic factors of LPA have not been elucidated. Methods. Data from the Surveillance, Epidemiology, and End Results (SEER) database of 4191 LPA patients were retrospectively analyzed and compared with non-LPA pulmonary ADC to explore the clinicopathological and prognosis features of LPA. Univariate and multivariate Cox proportional hazard models were performed to identify independent survival predictors for further nomogram development. The nomograms were validated using the concordance index, receiver operating characteristic curves, and calibration plots, as well as decision curve analysis, in both the training and validation cohorts. Results. Compared with non-LPA pulmonary ADC patients, those with LPA exhibited unique clinicopathological features, including more elderly and female patients, smaller tumor size, less pleural invasion, and lower histological grade and stage. Multivariate analyses showed that age, sex, race, tumor location, primary tumor size, pleural invasion, histological grade, stage, primary tumor surgery, and chemotherapy were independently associated with overall survival (OS) and cancer-specific survival (CSS) in patients with LPA. The nomograms showed good accuracy compared with the actual observed results and demonstrated improved prognostic capacity compared with the TNM stage. Conclusions. LPA is more frequently diagnosed in older people and women. LPA was inclined to be smaller in tumor size and lower in tumor grade and staging, which may indicate a favorable prognosis. The constructed nomograms accurately predict the long-term survival of LPA patients.

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