Intratumoral tertiary lymphoid structure (TLS) maturation is influenced by draining lymph nodes of lung cancer.

BACKGROUND: Tertiary lymphoid structure (TLS) is an organized infiltration of immune cells, showing features of germinal center (GC) commonly seen in secondary lymphoid organs. However, its relationship with tumor-draining lymph nodes (TDLNs) has not been studied and we hypothesized that TDLN may influence maturation of intratumoral TLS in non-small cell lung cancer (NSCLC). METHODS: Tissue slides of 616 patients that had undergone surgeries were examined. Cox proportional hazard regression model was used to assess risk factors of patients' survival, and logistic regression model was used for their relationship with TLS. Single-cell RNA-sequencing (scRNA-seq) was employed to explore transcriptomic features of TDLNs. Immunohistochemistry, multiplex immunofluorescence and flow cytometry were performed to analyze cellular composition. Cellular components of NSCLC samples from The Cancer Genome Atlas database were inferred with Microenvironment Cell Populations-counter (MCP-counter) method. Murine NSCLC models were used to dissect underlying mechanisms for relationship between TDLN and TLS maturation. RESULTS: While GC+ TLS was associated with better prognosis, GC- TLS was not. TDLN metastasis reduced the prognostic relevance of TLS, and was associated with less GC formation. Primary tumor sites showed reduced B cell infiltration in TDLN-positive patients, and scRNA-seq revealed diminished memory B cell formation in tumor-invaded TDLNs, together with an emphasis on weakened interferon (IFN)-γ response. Murine NSCLC models revealed that IFN-γ signaling is involved in memory B cell differentiation in TDLNs and GC formation in primary tumors. CONCLUSIONS: Our research emphasizes the influence of TDLN on intratumoral TLS maturation and suggests a role of memory B cells and IFN-γ signaling in this communication.

Comparison of efficiency and safety of conservative versus interventional management for primary spontaneous pneumothorax: A meta-analysis.

BACKGROUND: There is growing opinion that primary spontaneous pneumothorax (PSP) patients without hemodynamic compromise could be safely and successfully managed with observation alone. The aims of this meta-analysis were to estimate the safety and effectiveness of conservative treatment compared with that of interventional management as the initial treatment option for patients with PSP. METHODS: The PubMed, Embase and Cochrane library databases were systematically searched for randomized controlled trials (RCTs) and cohort studies (prospective or retrospective) until April 25, 2020, that compared conservative treatment and interventional treatment as the initial treatment for patients with PSP. The primary outcomes were success rates and recurrence rates. The secondary outcome was complication rates. Data extraction and quality assessment from eligible studies were independently conducted by two reviewers. RESULTS: 8 trials with a total of 1342 patients were identified. The success rates of conservative management were similar with interventional treatment, with a risk ratio 1.05 (95% confidence interval 0.94 to 1.17, I2 = 69.1%). There was no significant difference of recurrence rates between these two type managements. (RR, 1.43, 95% confidence interval 0.45 to 4.55, I2 = 86.7%). Complication rates were lower in conservative treatment group (13 of 215 [6.05%]) than in interventional treatment group (57 of 212, [26.89%]), although the difference did not reach statistical significance (RR, 0.15, 95% CI, 0.02 to 1.13, I2 = 56.7%). CONCLUSIONS: Results of the meta-analysis suggest that conservative treatment offers a safe and effective alternative as compared with interventional management as the initial treatment approach for patients with PSP. However, more randomized clinical trials are need to provide more strong evidence to confirm our results.