Search

Lung adenocarcinoma is the leading cause of cancer death. However, knowledge of the tumor immune microenvironment in early lung cancer patients, especially in comparison with the matched adjacent tissues, remains lacking. To characterize the tumor microenvironment (TME) of early-stage lung adenocarcinoma, we performed RNA-seq profiling on 58 pairs of minimally invasive adenocarcinoma (MIA) tumors and matched adjacent normal lung tissues. We observed over-expression and glycosylation of mucins, along with altered cytokine-cytokine interactions in MIA tumors. MIA tumors also exhibited an adaptive immune TME characterized by high CD4+ T-cell infiltration, high plasma B-cell activation, and low CD8+ T-cell infiltration. The high expression of markers for B cells, activated CD4+ T cells, and follicular helper T (Tfh) cells in bulk MIA samples and three independent single-cell RNA-seq datasets implied the formation of tertiary lymphoid structures (TLS). Multiplex immunohistochemistry (mIHC) staining of 22 MIA tumors validated TLS formation and revealed an enrichment of follicular regulatory T cells (Tfr) in TLS follicles, which may explain the lower CD8+ T-cell infiltration and attenuated anti-tumor immunity in MIA. Our study demonstrates how integrating tumor transcriptome analysis and pathology can characterize the TME and elucidate potential mechanisms of tumor immune evasion.

Objective(s) Lymph node status is vital for patients with small cell lung cancer (SCLC). We sought to evaluate the association between the number of lymph nodes examined (NLNE) and prognosis and nodal upstaging in stage I SCLC patients. Methods We queried the Surveillance, Epidemiology and End Results (SEER) database and our department for surgically treated patients with pathologic stage I SCLC to evaluate the correlation between NLNE and overall survival (OS). We further investigated the association between the NLNE and nodal upstaging in clinical stage I SCLC. Results A total of 878 patients with pathologic stage I SCLC were enrolled from the SEER database. Univariate and multivariate Cox regression analysis revealed that removing more than 6 lymph nodes was associated with significantly improved OS. We validated the prognostic impact from examining more than 6 nodes in pathologic stage I SCLC patients from our department. Logistic regression analysis found that removing more than 6 nodes increased the odds of nodal upstaging for clinical stage I SCLC. Conclusions Adequate nodal examination leads to survival benefits and accurate nodal staging. Our analysis indicated that examining more than 6 lymph nodes could confer better OS and predict nodal upstaging for stage I SCLC patients.

Summary: cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1−/− BMDM cells and in Trex1−/− mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases. : Li et al. have characterized a small-molecule cyclopeptide, astin C, which specifically inhibits cGAS-STING signaling as well as the innate inflammatory responses. This finding provides a way to potentially manipulate STING-mediated clinical diseases. Keywords: cGAS, STING, IRF3, TBK1, HSV-1, cyclopeptide, astin C, therapeutic target, innate immunity, autoimmune diseases