Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma.

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.

Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study.

OBJECTIVES: To compare neoadjuvant chemotherapy (NAC) plus concurrent chemoradiotherapy (CCRT) to CCRT alone in children and adolescents (age ≤ 18 years) with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC, stage III-IVA). MATERIALS AND METHODS: 195 CA-LANPC patients who were treated through CCRT with or without NAC between 2008 and 2018 were enrolled in this study. A matched cohort composed of CCRT patients and NAC-CCRT patients was generated by propensity score matching (PSM) at a 1:2 ratio. Survival outcomes and toxicities were compared between the CCRT group and NAC-CCRT group. RESULTS: Of the 195 patients, 158 (81%) received NAC plus CCRT, and 37 (19%) received CCRT alone. The NAC-CCRT group had higher EBV DNA levels (≥ 4000 copy/mL), more advanced TNM stage (stage IV disease), and lower incidence of a high radiation dose (> 6600 cGy) than the CCRT group. To avoid bias in treatment selection within retrospectively analysis, 34 patients from the CCRT group were matched with 68 patients from the NAC-CCRT group. In the matched cohort, the 5-year DMFS rate was 94.0% in the NAC-CCRT group versus 82.4% in the CCRT group, with marginal statistical significance (HR = 0.31; 95%CI 0.09-1.10; P = 0.055). During treatment, the accumulate incidence of severe acute toxicities (65.8% vs 45.9%; P = 0.037) in the NAC-CCRT group was higher than the CCRT group. However, the CCRT group had significantly higher accumulate incidence of severe late toxicities (30.3% vs 16.8%; P = 0.041) than the NAC-CCRT group. CONCLUSIONS: Addition of NAC to CCRT tended to improve long-term DMFS in CA-LANPC patients with acceptable toxicity. However, relative randomized clinical trial is still needed in the future.

Implications of Necroptosis for Cardiovascular Diseases.

Necroptosis is a non-apoptotic programmed cell death pathway, which causes necrosis-like morphologic changes and triggers inflammation in the surrounding tissues. Accumulating evidence has demonstrated that necroptosis is involved in a number of pathological processes that lead to cardiovascular diseases. However, the exact molecular pathways linking them remain unknown. Herein, this review summarizes the necroptosis-related pathways involved in the development of various cardiovascular diseases, including atherosclerosis, cardiac ischemia-reperfusion injury, cardiac hypertrophy, dilated cardiomyopathy and myocardial infarction, and may shed light on the diagnosis and treatment of these diseases.

Plasma Homocysteine Levels Are Associated With Circadian Blood Pressure Variation in Chinese Hypertensive Adults.

BACKGROUND: Homocysteine-lowering intervention with folate was recently shown to be able to increase day-night difference of blood pressure (BP) in humans indicating a potential relationship between homocysteine and circadian BP variation. We thus sought to investigate the association between plasma total homocysteine level (tHcy) and circadian BP variation in hypertensive adults. METHODS: We enrolled 244 eligible dipping and 249 nondipping BP status adults from 560 adults who were randomly sampled from 5,233 Chinese hypertensive adults who received ambulatory BP monitoring (ABPM). We further enrolled 390 adults with CC/CT genotypes of the methylenetetrahydrofolate reductase (MTHFR) and 79 TT genotype who received ABPM at the same time from 1858 hypertensive adults with MTHFR polymorphisms detection. RESULTS: Plasma tHcy in nondippers was significantly higher than dippers (P < 0.001). Simple linear analysis revealed that tHcy significantly correlated with nocturnal systolic BP fall (r = -0.145, P = 0.001) and diastolic BP fall (r = -0.141, P = 0.002). Multivariate logistic regression analysis further identified tHcy as an independent factor correlated with the presence of nondipping BP status in hypertensive adults (odds ratio: 1.873, 95% confidence interval: 1.171-2.996, P = 0.009). The percentage of dipping BP status was 19.49% or 8.86% and the percentage of nondipping BP status was 80.51% or 91.14% in CC/CT or TT genotypes, respectively. The above different between CC/CT and TT genotypes was significant (P = 0.024). CONCLUSIONS: These results indicated that high homocysteine levels associate with disturbed circadian BP variation in Chinese hypertensive adults.