Lymph node metastasis, the leading cause of mortality in esophageal squamous carcinoma (ESCC) with a highly complex tumor microenvironment, remains underexplored. Here, the transcriptomes of 85 263 single cells are analyzed from four ESCC patients with lymph node metastases. Strikingly, it is observed that the metastatic microenvironment undergoes the emergence or expansion of interferon induced IFIT3+ T, B cells, and immunosuppressive cells such as APOC1+APOE+ macrophages and myofibroblasts with highly expression of immunoglobulin genes (IGKC) and extracellular matrix component and matrix metallopeptidase genes. A poor‐prognostic epithelial‐immune dual expression program regulating immune effector processes, whose activity is significantly enhanced in metastatic malignant epithelial cells and enriched in CD74+CXCR4+ and major histocompatibility complex (MHC) class II genes upregulated malignant epithelia cells is discovered. Comparing with primary tumor, differential intercellular communications of metastatic ESCC microenvironment are revealed and furtherly validated via multiplexed immunofluorescence and immunohistochemistry staining, which mainly rely on the crosstalk of APOC1+APOE+ macrophages with tumor and stromal cell. The data highlight potential molecular mechanisms that shape the lymph‐node metastatic microenvironment and may inform drug discovery and the development of new strategies to target these prometastatic nontumor components for inhibiting tumor growth and overcoming metastasis to improve clinical outcomes.

Background and aim Standard chemotherapy has limited clinical efficacy in patients with esophageal cancer and there is a significant and unmet clinical need for effective treatment options for these patients. The aim of this study was to compare the clinical efficacy of the novel, targeted drug apatinib combined with docetaxel, and docetaxel combined with S-1 as second- or further-line treatment for patients with advanced esophageal cancer. Methods We enrolled 33 patients with advanced esophageal cancer in chemotherapy group or apatinib combined with chemotherapy group in this retrospective study. Apatinib (500 mg) was taken orally once daily; docetaxel was administered at a dose of 75 mg/m 2 ; and S-1 was optional at a dose of 40–60 mg, based on body surface area. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence and severity of adverse events (AEs). Results No complete response was observed in the two groups. However, two and five patients achieved partial response in the chemotherapy group and the apatinib combined with chemotherapy group, respectively. The ORR and DCR for the chemotherapy group was 11.1% and 33.3%, respectively. In the apatinib combination group, ORR and DCR was 88.9% and 93.3%, respectively. Anemia (11.1%) and neutropenia (5.6%) were the most frequent grade III/IV AEs observed in the chemotherapy group. In the apatinib combination group, the most frequent grade III/IV AEs were anemia (13.3%), hypertension (6.7%), and proteinuria (6.7%). Median PFS was significantly longer in the apatinib combination group than in the chemotherapy group (175 days vs 85 days, P =0.01). Conclusion The combination of apatinib and docetaxel has a manageable toxicity profile and may prolong survival. Therefore, this combination may be used as as second- or further-line treatment for patients with advanced esophageal cancer.

Germline polymorphisms are linked with differential survival outcomes in cancers but are not well studied in nasopharyngeal carcinoma (NPC). Here, a two-phase association study is conducted to discover germline polymorphisms that are associated with the prognosis of NPC. The discovery phase includes two consecutive hospital cohorts of patients with NPC from Southern China. Exome-wide genotypes at 246 173 single nucleotide polymorphisms (SNPs) are determined, followed by survival analysis for each SNP under Cox proportional hazard regression model. Candidate SNP is replicated in another two independent cohorts from Southern China and Singapore. Meta-analysis of all samples (n = 5553) confirms that the presence of rs1131636-T, located in the 3′-UTR of RPA1, confers an inferior overall survival (HR = 1.33, 95% CI = 1.20-1.47, P = 6.31 × 10 −8 ). Bioinformatics and biological assays show that rs1131636 has regulatory effects on upstream RPA1. Functional studies further demonstrate that RPA1 promotes the growth, invasion, migration, and radioresistance of NPC cells. Additionally, miR-1253 is identified as a suppressor for RPA1 expression, likely through regulation of its binding affinity to rs1131636 locus. Collectively, these findings provide a promising biomarker aiding in stratifying patients with poor survival, as well as a potential drug target for NPC.

Esophageal cancer (EC) is the eighth most common type of cancer worldwide and ranks sixth among the causes of cancer-related mortality. Due to the high mortality rate and poor treatment efficacy for EC, millions of individuals succumb to this disease; thus, the identification of novel treatment targets is of utmost importance and urgency. In recent years, there have been advances if therapies targeting cell cycle regulators. p21 is a type of cell cycle regulator that plays a dual role in tumor cells, as it can not only regulate the cell cycle, induce apoptosis and inhibit cell proliferation, but can also protect cells from apoptosis. It has been found that p21 often exerts a tumor-suppressive effect on EC, which provides a basis for its use as a treatment target for EC. Therefore, the aim of the present study was to review the function of p21 and its potential value as a therapeutic target for EC.

Esophageal cancer (EC) is the eighth most common type of cancer and the sixth leading cause of cancer-related deaths worldwide. At present, the clinical treatment for EC is based mainly on radical surgery, chemotherapy, and radiotherapy. However, due to the limited efficacy of conventional treatments and the serious adverse reactions, the outcome is still unsatisfactory (the 5-year survival rate for patients is less than 25%). Thus, it is extremely important and urgent to identify new therapeutic targets. The concept of tumor microenvironment (TME) has attracted increased attention since it was proposed. Recent studies have shown that TME is an important therapeutic target for EC. Microenvironment-targeting therapies such as immunotherapy and antiangiogenic therapy have played an indispensable role in prolonging survival and improving the prognosis of patients with EC. In addition, many new drugs and therapies that have been developed to target microenvironment may become treatment options in the future. We summarize the microenvironment of EC and the latest advances in microenvironment-targeting therapies in this review.