Concurrent chemoradiotherapy (CRT) is regarded as the standard treatment for inoperable esophageal cancers (EC). It is still controversial whether consolidation chemotherapy (CCT) or induction chemotherapy (IC) is beneficial for the patients who received CRT. Therefore, we carried out a retrospective analysis at our institution. A total of 186 inoperable EC patients from 20 October 2017 to 7 June 2021 who have previously received CRT were included in our study. The patients were divided into IC + CRT (n = 52), CCRT (n = 64), and CRT + CCT (n = 70) groups according to whether they received induction chemotherapy, consolidation chemotherapy, or not. We used Kaplan–Meier statistics to analyze their 1-, 2-, and 3-year OS. The median follow-up time for the whole group was 14.15 months. The 1-, 2-, 3- year overall survival (OS) for the CCRT group were 72.2%, 52.5%, and 29.5%, and 50.9%, 37.5%, and 25% for the IC + CRT group (p > 0.05). For the CRT + CCT group,1-, 2-, and 3-year OS were 89.8%, 59.0%, and 42.5% (p < 0.05). Adverse reactions in the three groups were mainly graded 0–3. The difference between the three groups was not statistically significant (p > 0.05). For non-surgical EC patients who received CRT, CCT after CRT but not IC before CRT can improve 1-, 2-, and 3-year OS with a low incidence of associated severe adverse effects. As a result, the addition of consolidation chemotherapy to chemoradiotherapy has significant prognostic advantages for inoperable EC patients.

Purpose. Cervical cancer (CC) is one of the most common gynecologic neoplasms. Hypoxia is an essential trigger for activating immunosuppressive activity and initiating malignant tumors. However, the determination of the role of immunity and hypoxia on the clinical outcome of CC patients remains unclear. Methods. The CC independent cohort were collected from TCGA database. Consensus cluster analysis was employed to determine a molecular subtype based on immune and hypoxia gene sets. Cox relevant analyses were utilized to set up a risk classifier for prognosis assessment. The underlying pathways of classifier genes were detected by GSEA. Moreover, we conducted CIBERSORT algorithm to mirror the immune status of CC samples. Results. We observed two cluster related to immune and hypoxia status and found the significant difference in outcome of patients between the two clusters. A total of 251 candidate genes were extracted from the two clusters and enrolled into Cox relevant analyses. Then, seven hub genes (CCL20, CXCL2, ITGA5, PLOD2, PTGS2, TGFBI, and VEGFA) were selected to create an immune and hypoxia-based risk classifier (IHBRC). The IHBRC can precisely distinguish patient risk and estimate clinical outcomes. In addition, IHBRC was closely bound up with tumor associated pathways such as hypoxia, P53 signaling and TGF β signaling. IHBRC was also tightly associated with numerous types of immunocytes. Conclusion. This academic research revealed that IHBRC can be served as predictor for prognosis assessment and cancer treatment estimation in CC.

Background: Brain metastasis (BrM) has been a challenge for lung cancer treatment, but the mechanisms underlying lung cancer BrM remain elusive. This study aims to dissect cellular components and their spatial distribution in human BrM tumors of lung adenocarcinoma (LUAD) and identify potential therapeutic targets. Methods: We performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) on three LUAD BrMs, and validated our findings using public scRNA-seq data of 10 LUAD BrMs. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) and functional experiments were employed for experimental studies. Results: By combining scRNA-seq and ST, our analysis revealed the inter- and intra-tumoral heterogeneity of cellular components and their spatial localization within LUAD BrMs. Through RNA velocity and transcription factor (TF) regulatory activity analyses, we identified ATF3 as a potential regulator of the mesenchymal-epithelial transition (MET) program, which plays crucial roles in the colonization of tumor cells at metastatic sites. Furthermore, we demonstrated that knockdown of ATF3 significantly inhibited cancer cell proliferation while promoting cancer cell migration. Mechanistically, ATF3 knockdown could reverse the MET program. Additionally, we revealed that LGALS3/ANXA2-mediated cell-cell interaction between macrophage and tumor cells may also promote the MET program. Conclusions: Our study provides a single-cell atlas of the cellular composition in BrM of LUAD and identifies ATF3 as a potential therapeutic target for BrM treatment.

Most small cell lung cancers (SCLCs) exhibit low immunogenicity and intrinsic resistance to immunotherapy, yet the underlying mechanisms remain poorly understood. Here, we identify CREBBP loss, a frequent genetic alteration in SCLC, as a key suppressor of tumor cell-intrinsic immune responses that drives an immune-cold tumor microenvironment in Rb1/Trp53 -driven autochthonous mouse models. Consistently, Crebbp deletion promotes immune escape in syngeneic SCLC models. Mechanistically, Crebbp loss suppresses Sting and major histocompatibility complex class-I expression by reducing histone H3 acetylation. Notably, HDAC inhibition restores histone acetylation, reactivates these silenced genes, and induces tumor cell-intrinsic immune responses. Moreover, pharmacological HDAC inhibition synergizes with immune checkpoint blockade to suppress tumor growth in both Crebbp -mutant and Crebbp -wild-type SCLCs, with a more prominent effect in Crebbp -mutant tumors. Collectively, these findings establish CREBBP loss as a key mechanism of immune evasion and immunotherapy resistance in SCLC, highlighting HDAC inhibition as a promising strategy to enhance immunotherapy efficacy.

Background: Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by an intrinsic resistance to immunotherapy, primarily due to its low immunogenicity and immune-cold tumor microenvironment. The mechanisms underlying this resistance remain poorly understood. Methods: A systematic screen of 796 epigenetic regulators was performed to identify candidate genes associated with effector CD8⁺ T cell infiltration and clinical outcomes following chemoimmunotherapy in SCLC. This analysis integrated several public SCLC datasets, including single-cell RNA sequencing (scRNA-seq) data from 20 SCLC tumors, bulk RNA-seq data from the IMpower133 cohort, proteomic profiles from the TU-SCLC cohort, and an independent scRNA-seq dataset of 39 SCLC tumors. In vitro and in vivo functional experiments were conducted to investigate the role of the candidate genes in SCLC. Results: The epigenetic regulator TAF1 emerged as a key candidate, with its expression negatively correlating with effector CD8⁺ T cell infiltration in SCLC. Clinically, patients with low TAF1 expression in tumors showed better outcomes following atezolizumab-based chemoimmunotherapy, particularly in ASCL1-high tumors. Additionally, TAF1 expression was inversely correlated with MHC-I expression. Knockdown of TAF1 in SCLC cells restored MHC-I expression, suppressed tumor growth in immunocompetent mice, and increased CD8⁺ T cell infiltration. Conclusions: TAF1 functions as a potential epigenetic suppressor of MHC-I expression in SCLC. Targeting TAF1 may represent a promising therapeutic strategy to enhance immunotherapy efficacy in SCLC.