Background and objectives: The safety and effectiveness of minimally invasive esophagectomy (MIE) in comparison with the open esophagectomy (OE) remain uncertain in esophageal cancer treatment. The purpose of this meta-analysis is to compare the outcomes of the two surgical modalities. Methods: Searches were conducted in MEDLINE, EMBASE, and ClinicalTrials.gov with the following index words: “esophageal cancer”, “VATS”, “MIE”, “thoracoscopic esophagectomy”, and “open esophagectomy” for relative studies that compared the effects between MIE and OE. Random-effect models were used, and heterogeneity was assessed. Results: A total of 20 studies were included in the analysis, consisting of four randomized controlled trials and 16 prospective studies. MIE has reduced operative blood loss (P=0.0009) but increased operation time (P=0.009) in comparison with OE. Patients get less respiratory complications (risk ratio =0.74, 95% CI =0.58–0.94, P=0.01) and better overall survival (hazard ratio =0.54, 95% CI =0.42–0.70, P<0.00001) in the MIE group than the OE group. No statistical difference was observed between the two groups in terms of lymph node harvest, R0 resection, and other major complications. Conclusion: MIE is a better choice for esophageal cancer because patients undergoing MIE may benefit from reduced blood loss, less respiratory complications, and also improved overall survival condition compared with OE. However, more randomized controlled trials are still needed to verify these differences.

The existence of tumor heterogeneity and complex carcinogenic mechanisms in lung adenocarcinoma (LUAD) make the most commonly used TNM staging system unable to well-interpret the prognosis of patients. Using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA) database, we constructed an immune signature based on a multivariate Cox analysis (stepwise model). We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients according to the pRRophetic algorithm. Gene-set variation analysis (GSVA) was used to reveal pathway enrichment between groups. Moreover, immune microenvironment landscape was described by single-sample gene-set enrichment analysis (ssGSEA) and CIBERSORT and systematically correlated with genomic of these patients. A prognostic nomogram combining the immune signature and TNM stage to predict the prognosis was developed by multivariate Cox regression. The novel signature with four immune-related genes (MAL, MS4A1, OAS1, and WFDC2) had good robustness, which can accurately distinguish between high- and low-risk patients. Compared with low-risk patients, high-risk patients with a worse prognosis (5-year OS: 46.5 vs. 59.4%, p = 0.002) could benefit more from immunotherapy and the application of common chemotherapeutic agents such as cisplatin and paclitaxel (Wilcoxon test, all p < 0.05). There were significant differences in tumor immune microenvironment and metabolic pathways between the two groups. Additionally, the constructed nomogram had reliable predictive performance with the C-index of 0.725 (95% CI = 0.668–0.781) in the development set (n = 500), 0.793 (95% CI = 0.728–0.858) in the internal validation set (n = 250) and 0.679 (95% CI = 0.644–0.714) in the external validation set (n = 442). The corresponding calibration curves also showed good consistency. To sum up, we developed an immune-related gene signature and comprehensively evaluated LUAD immune landscape and metabolic pathways. Effective differentiation of high- and low-risk patients and accurate construction of nomogram would be helpful to the development of individualized treatment strategies.

Cancer has been a major public health problem that has threatened human life worldwide throughout history. The main causes that contribute to the poor prognosis of cancer are metastasis and recurrence. Cancer stem cells are a group of tumor cells that possess self-renewal and differentiation ability, which is a vital cause of cancer metastasis and recurrence. Long non-coding RNAs refer to a class of RNAs that are longer than 200 nt and have no potential to code proteins, some of which can be specifically expressed in different tissues and different tumors. Long non-coding RNAs have great biological significance in the occurrence and progression of cancers. However, how long non-coding RNAs interact with cancer stem cells and then affect cancer metastasis and recurrence is not yet clear. Therefore, this review aims to summarize recent studies that focus on how long non-coding RNAs impact tumor occurrence and progression by affecting cancer stem cell self-renewal and differentiation in liver cancer, prostate cancer, breast cancer, and glioma.

Inflammation is a key characteristic of all stages of tumor development, including tumor initiation, progression, malignant transformation, invasion, and metastasis. Inflammasomes are an important component of the inflammatory response and an indispensable part of the innate immune system. Inflammasomes regulate the nature of infiltrating immune cells by signaling the secretion of different cytokines and chemokines, thus regulating the anti-tumor immunity of the body. Inflammasome expression patterns vary across different tumor types and stages, playing different roles during tumor progression. The complex diversity of the inflammasomes is determined by both internal and external factors relating to tumor establishment and progression. Therefore, elucidating the specific effects of different inflammasomes in anti-tumor immunity is critical for promoting the discovery of inflammasome-targeting drugs. This review focuses on the structure, activation pathway, and identification methods of the NLRP3, NLRC4, NLRP1 and AIM2 inflammasomes. Herein, we also explore the role of inflammasomes in different cancers and their complex regulatory mechanisms, and discuss current and future directions for targeting inflammasomes in cancer therapy. A detailed knowledge of inflammasome function and regulation may lead to novel therapies that target the activation of inflammasomes as well as the discovery of new drug targets.

Immunogenic cell death (ICD) plays a crucial role in triggering the antitumor immune response in the tumor microenvironment (TME). Recently, considerable attention has been dedicated to ferroptosis, a type of ICD that is induced by intracellular iron and has been demonstrated to change the immune desert status of the TME. However, among cancers that are characterized by an immune desert, such as prostate cancer, strategies for inducing high levels of ferroptosis remain limited. Radiated tumor cell-derived microparticles (RMPs) are radiotherapy mimetics that have been shown to activate the cGAS-STING pathway, induce tumor cell ferroptosis, and inhibit M2 macrophage polarization. RMPs can also act as carriers of agents with biocompatibility. In the present study, we designed a therapeutic system wherein the ferroptosis inducer RSL-3 was loaded into RMPs, which were tested in in vitro and in vivo prostate carcinoma models established using RM-1 cells. The apoptosis inducer CT20 peptide (CT20p) was also added to the RMPs to aggravate ferroptosis. Our results showed that RSL-3- and CT20p-loaded RMPs (RC@RMPs) led to ferroptosis and apoptosis of RM-1 cells. Moreover, CT20p had a synergistic effect on ferroptosis by promoting reactive oxygen species (ROS) production, lipid hydroperoxide production, and mitochondrial instability. RC@RMPs elevated dendritic cell (DC) expression of MHCII, CD80, and CD86 and facilitated M1 macrophage polarization. In a subcutaneously transplanted RM-1 tumor model in mice, RC@RMPs inhibited tumor growth and prolonged survival time via DC activation, macrophage reprogramming, enhancement of CD8⁺ T cell infiltration, and proinflammatory cytokine production in the tumor. Moreover, combination treatment with anti-PD-1 improved RM-1 tumor inhibition. This study provides a strategy for the synergistic enhancement of ferroptosis for prostate cancer immunotherapies. Graphical Abstract

Background: Research on patients with lung cancer as a second primary malignancy (LCSPM) remains limited. This study aims to determine the clinical characteristics, prognosis, and temporal relationship of other cancers to lung cancer in these patients. Methods: This study retrospectively analyzed 3465 patients with dual primary cancers from the 5253 patients with LCSPM retrieved from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015. Results: 2285 eligible patients were further analyzed in this study cohort with 59.3% of 1-year OS, 34.7% of 3-year OS, and 25.2% of 5-year OS. The most common first primary cancer (FPC) in dual primary cancer patients with LCSPM was prostate cancer, followed by female breast cancer and urinary bladder cancer. In the entire study population, the median interval between the two primary malignancies was 21 months (range: 3.5–52 months). Age, sex, FPC location, surgery, stage, and histology of lung cancer were regarded as independent prognostic factors for these patients. The prognosis of patients with urinary bladder cancer as FPC was the worst in the univariate (p = 0.024) and multivariate (p < 0.001) Cox analyses. Lung cancer-directed surgery could significantly improve long-term survival (HR = 0.22, p < 0.001). Additionally, the C-index of the established nomogram with acceptable calibration curves was 0.760 (95% CI: 0.744–0.776) in the training cohort and was 0.759 (95% CI: 0.737–0.781) in the validation cohort, showing an ideal model discrimination ability. The corresponding decision curve analysis (DCA) indicated the nomogram had relatively ideal clinical utility. Conclusions: Cancer patients still have the risk of developing a new primary lung cancer. Close, lifelong follow-up is recommended for all these patients. Early detection for surgical treatment will significantly improve the prognosis of dual primary cancer patients with LCSPM. The nomogram developed to predict 1-, 3-, and 5-year OS rates has relatively good performance.