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Abstract Intra‐tumour immune infiltration is a crucial determinant affecting immunotherapy response in non‐small cell lung cancer (NSCLC). However, its phenotype and related spatial structure have remained elusive. To overcome these restrictions, we undertook a comprehensive study comprising spatial transcriptomic (ST) data (28 712 spots from six samples). We identified two distinct intra‐tumour infiltration patterns: immune exclusion (characterised by myeloid cells) and immune activation (characterised by plasma cells). The immune exclusion and immune activation signatures showed adverse and favourable roles in NSCLC patients' survival, respectively. Notably, CD14+APOE+ cells were recognised as the main cell type in immune exclusion samples, with increased epithelial‒mesenchymal transition and decreased immune activities. The co‐location of CD14+APOE+ cells and MMP7+ tumour cells was observed in both ST and bulk transcriptomics data, validated by multiplex immunofluorescence performed on 20 NSCLC samples. The co‐location area exhibited the upregulation of proliferation‐related pathways and hypoxia activities. This co‐localisation inhibited T‐cell infiltration and the formation of tertiary lymphoid structures. Both CD14+APOE+ cells and MMP7+ tumour cells were associated with worse survival. In an immunotherapy cohort from the ORIENT‐3 clinical trial, NSCLC patients who responded unfavourably exhibited higher infiltration of CD14+APOE+ cells and MMP7+ tumour cells. Within the co‐location area, the MK, SEMA3 and Macrophage migration inhibitory factor (MIF) signalling pathway was most active in cell‒cell communication. This study identified immune exclusion and activation patterns in NSCLC and the co‐location of CD14+APOE+ cells and MMP7+ tumour cells as contributors to immune resistance.

Abstract Background The aim of the study was to explore the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with non‐small cell lung cancer (NSCLC). Methods Studies that enrolled NSCLC patients treated with two lines of ICIs were included using four databases. The initial line (1L‐) and subsequent lines (2L‐) of ICIs were defined as 1L‐ICI and 2L‐ICI, respectively. Results A total of 17 studies involving 2100 patients were included. The pooled objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), and median overall survival (mOS) for 2L‐ICIs were 10%, 50%, 3.0 months, and 13.1 months, respectively. The 2L‐ICI discontinuation rates caused by toxicities ranged from 0% to 23.5%. Original data were extracted from six studies, covering 89 patients. Patients in whom 1L‐ICIs were discontinued following clinical decision (the mPFS of 2L‐ICIs was not reach) achieved a more prolonged mPFS of 2L‐ICIs than those due to toxicity (5.2 months) and progressive disease (2.1 months) (p

Abstract Seismic anisotropy in the upper mantle reveals geodynamic processes and the tectonic evolution of the Earth. The two most powerful methods, surface wave tomography, and shear‐wave splitting observations, cannot investigate the deep local anisotropy with good vertical and lateral resolution, resulting in poor constraints on plate deformation processes of the complex plate boundary beneath the Southern California region. Here, we show that the amplitude ratio of translational displacement and rotation makes it possible to retrieve the local anisotropy in the upper mantle. Azimuthal anisotropy in the asthenosphere is well determined and resolved in lateral and vertical directions. The fast axis retrieved from amplitude observations indicates the local rapid changes in plate deformation and complex pattern of mantle flow, which is compatible with the distributions of horizontal mantle flow illuminated by geodetic measurements, providing new insights on geodynamic processes of the Southern California region.

Abstract Background Real‐world application of osimertinib with antiangiogenic agents in non‐small cell lung cancer (NSCLC) is common, but the efficacy data are rarely reported. Methods To obtain an objective efficacy report of different real‐world treatment models of osimertinib and antiangiogenic agents. Results A total of 54 patients with NSCLC were enrolled into the study. Twelve (22.2%) who received a combination of antiangiogenic agents, when there was a trend of osimertinib resistance but did not reach imageology progressive disease (PD), were assigned to Group A, with a median overall survival (OS) and progression‐free survival (PFS) of 48.0 (95% CI, not reached) and 21.0 (95% CI: 16.7–25.3) months, respectively. Thirty (55.6%) who received a combination of antiangiogenic agents when there was imageology PD during treatment with osimertinib were assigned to Group B, with a median OS and PFS of 31.8 (95% CI: 26.6–37.1) and 9.2 (95% CI: 5.9–12.6) months, respectively. Twelve (22.2%) who received a combination of antiangiogenic agents at the initial treatment with osimertinib were assigned to Group C, with a median OS and PFS of 28.5 (95% CI: 15.2–41.8) and 15.3 (95% CI: 7.9–22.7) months, respectively. Patients in Group A achieved a significant prolonged median PFS (p

Abstract Aim There are still patients of stage I lung adenocarcinoma (ADC) suffering from local or distant recurrence. Herein we conducted a meta‐analysis to investigate the prognostic value of tumor spread through air space (STAS), a new form of invasion pattern, in patients with pathologically confirmed stage I lung ADC. Methods Related literature was searched using PubMed, Embase, Cochrane Library, and Web of Science databases from the inception dates to September 4, 2021. Recurrence‐free survival (RFS) and overall survival (OS) were set as primary outcome endpoints. In addition, subgroup analyses on operation mode, edition of the American Joint Committee on Cancer TNM staging, sample size, and research regions were also investigated. Results A total of 17 studies involving 9785 patients were included. The presence of STAS was detected in 31.2% of patients and was associated with poor RFS (adjusted hazard ratio [HR] = 1.93, p

Background: Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. Methods: In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. Results: Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 109/L (range 18–219) among patients who received rhTPO and 73 × 109/L (range 42–197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count