The response to programmed death-1 (PD-1) blockade varies in hepatocellular carcinoma (HCC). We utilize a panel of 16 serum factors to show that a circulating level of serum amyloid A (SAA) > 20.0 mg/L has the highest accuracy in predicting anti-PD-1 resistance in HCC. Further experiments show a correlation between peritumoral SAA expression and circulating SAA levels in patients with progressive disease after PD-1 inhibition. In vitro experiments demonstrate that SAA induces neutrophils to express PD-L1 through glycolytic activation via an LDHA/STAT3 pathway and to release oncostatin M, thereby attenuating cytotoxic T cell function. In vivo, genetic or pharmacological inhibition of STAT3 or SAA eliminates neutrophil-mediated immunosuppression and enhances antitumor efficacy of anti-PD-1 treatment. This study indicates that SAA may be a critical inflammatory cytokine implicated in anti-PD-1 resistance in HCC. Targeting SAA-induced PD-L1⁺ neutrophils through STAT3 or SAA inhibition may present a potential approach for overcoming anti-PD1 resistance.

Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

The existence of cancer stem cells (CSCs) is central to the pathogenesis and therapeutic target of human hepatocellular carcinoma. The aim of this study was to investigate the effects of casticin on epithelial‑mesenchymal transition (EMT) of liver cancer stem cells (LCSCs) derived from the SMMC‑7721 cell line. Our results demonstrated that CD133+ sphere‑forming cells (SFCs) sorted from the SMMC‑7721 cell line not only possessed a higher capacity to form tumor spheroids in vitro, but also had a greater potential to form tumors when implanted in Balb̸c‑nu mice, indicating that CD133+ SFCs possessed similar traits to LCSCs. Casticin increased the expression levels of E‑cadherin and decreased those of N‑cadherin in LCSCs. Treatment of LCSCs with casticin for 48 h also decreased the levels of the EMT‑associated transcription factor, Twist. Overexpression of Twist attenuated the casticin‑induced regulation of E‑cadherin and N‑cadherin protein expression, as well as the EMT capacity of LCSCs. In conclusion, CD133+ SFCs of the SMMC‑7721 cell line may represent a subpopulation of LCSCs with the characteristics of EMT. Furthermore, casticin targeted LCSCs through the inhibition of EMT by downregulating Twist.

Background: Nutritional deterioration (ND) during radiotherapy (RT) for esophageal cancer is common, yet the optimal timing for proactive supportive care remains unclear. We characterized time-resolved nutritional trajectories, examined baseline factors associated with deterioration, and translated the findings into a patient-facing digital prototype. Methods: In this prospective longitudinal cohort, 123 patients underwent nutritional assessment at five timepoints (admission, RT1, RT14, RT20, and discharge) using the Patient-Generated Subjective Global Assessment (PG-SGA), serum albumin, and total protein. ND was defined as an upward shift in PG-SGA risk category (0–3/4–8/≥9) from admission to discharge. Sleep was assessed by baseline interview, the Pittsburgh Sleep Quality Index (PSQI), and exploratory wearable measures. Logistic regression was used to identify baseline factors associated with ND. Complementary continuous-change analysis and linear mixed-effects modeling were additionally performed to characterize deterioration magnitude and longitudinal trajectories. Exploratory correlations assessed sleep–nutrition associations. Based on the findings, a digital prototype (“Esophageal Care Companion”) was developed with risk-aware onboarding and phase-specific monitoring prompts. Results: PG-SGA increased from 4.59 ± 3.66 at admission to 6.95 ± 3.48 at RT20 ( p < 0.001), with concordant declines in albumin and total protein. ND occurred in 40.7% (50/123). In the primary categorical model, baseline sleep problems were associated with higher odds of ND [adjusted odds ratio (aOR) 2.48; p = 0.034], as was N3 nodal stage (aOR 3.56; p = 0.022). In complementary analyses, N3 remained associated with greater PG-SGA worsening and a distinct longitudinal nutritional trajectory, whereas the sleep signal was less consistent across continuous and longitudinal models. Sleep measures showed exploratory phase-specific associations with nutritional biomarkers, including RT14 rapid eye movement sleep duration with albumin ( r = 0.258; p = 0.004) and discharge PSQI with PG-SGA ( r = 0.276; p = 0.002). Conclusion: Nutritional risk worsened during esophageal cancer RT, particularly in the mid-to-late treatment phase, supporting RT14–RT20 as a clinically relevant window for intensified assessment and supportive-care escalation. Advanced nodal stage emerged as a robust marker of less favorable nutritional trajectory. Baseline sleep problems may serve as a low-burden observational risk signal but should be interpreted cautiously. The prototype demonstrates the feasibility of translating phase-aware risk monitoring into digital supportive care.

Background: The direct and indirect roles of the cell cycle in immunology of the tumor microenvironment (TME) are topics of intense scientific interest. Therefore, this study aimed to investigate the knowledge domain and hotspots related to the cell cycle for cancer immunology applications. Material/Methods: The Web of Science Core Collection (WoSCC) was used as a powerful tool for identifying articles related to cell cycle for cancer immunology applications. Co-occurrence relationships were examined with R, VOSviewer, and CiteSpace software. Related research hotspots and possible future trends were also examined. Results: A total of 1844 qualified English-language documents were obtained in WoSCC between 1999 and 2022, with a 7.66% annual growth rate. These eligible studies were co-authored by 2246 institutions in 51 countries/regions, with the greatest article number being published in the United States (36%, 664/1844), followed by China (19%, 351/1844) and Germany (4.5%, 83/1844). The top 3 institutions with the most publications and the top 3 academic journals (n=390 in total) on this topic that published the most articles were identified. Key nodes from the co-cited network were aggregated and identified to reveal the shift in cell cycle for cancer immunology applications. Notably, the current research hotspots in this field include "tumor progression", "chemotherapy", "resistance", "clinical trial", and "target population". Conclusions: This study revealed field profiles, research hotspots, and future directions of cell cycle dysregulation-related immunology, and the findings will offer a vigorous roadmap for further studies in the combination therapy of cell cycle inhibitors and immune checkpoint inhibitors for treating various cancers. Our results can shed more light on relevant research in this field.