Chimeric antigen receptor (CAR) cellular immunotherapy has emerged as a revolutionary modality in cancer treatment. CAR-T cell therapy has demonstrated remarkable efficacy against hematological malignancies; however, its application in solid tumors is significantly constrained by inadequate tumor infiltration, a profoundly immunosuppressive tumor microenvironment (TME), and pervasive antigen heterogeneity. Conversely, macrophages - innate immune cells inherently poised within tissues - exhibit superior tumor-tropic migration, potent phagocytic capability, and a unique capacity to remodel the TME, establishing CAR-engineered macrophages (CAR-M) as a highly promising next-generation therapeutic platform. Despite this considerable promise, the clinical translation of CAR-M faces several critical bottlenecks, including heterogeneity in cell sources, challenges in manufacturing standardization, risks of on-target/off-tumor toxicity, and the dynamic, immunosuppressive nature of the TME. This review offers a systematic and in-depth analysis of the current research landscape and engineering advances in CAR-M therapy. It comprehensively details the molecular evolution of CAR-M designs, spanning from early constructs to sophisticated logic-gated circuits and innovative in vivo generation strategies utilizing lipid nanoparticles (LNPs). We critically evaluate the applicability and limitations of various cellular sources, such as peripheral blood mononuclear cells (PBMCs), induced pluripotent stem cells (iPSCs), and the THP-1 cell line. Furthermore, the review elucidates the multimodal antitumor mechanisms of CAR-M, including the direct "phagocytosis-presentation-activation" cascade, synergistic potential with immune checkpoint blockade, and deep reprogramming of the immunosuppressive TME. By synthesizing the latest preclinical and emerging clinical evidence, this article underscores the distinctive advantages and delineates a translational roadmap for CAR-M development. It is intended to serve as an authoritative reference for the field, providing strategic insights into intelligent receptor design, precision biomanufacturing, and rational combination therapies aimed at overcoming the enduring barriers in solid tumor immunotherapy.

Gastric mucinous adenocarcinoma (GMC) is a rare subtype of gastric cancer characterized by excessive mucus production, aggressive biological behavior, and poor prognosis, with most patients presenting with metastatic disease at initial diagnosis and losing the opportunity for curative resection. Currently, there are no standardized diagnostic and treatment guidelines for metastatic GMC in the conversion therapy setting, and the therapeutic effect of conventional chemotherapy remains unsatisfactory. Herein, we present a 69-year-old male patient diagnosed with HER2-negative, TMB-H advanced GMC, with intraperitoneal and retroperitoneal lymph node metastases. The patient was initially deemed unresectable by the multidisciplinary team (MDT) but opted for conversion therapy due to a strong willingness for treatment and good performance status (ECOG-PS=0). He received 6 cycles of FLOT chemotherapy combined with nivolumab, achieving partial response (PR) per RECIST 1.1. Subsequent laparoscopic distal gastric subtotal resection (D2+ lymphadenectomy) was performed, and postoperative pathology revealed a near pathological complete response (Mandard-TRG1) with no lymph node metastases (0/21), pathologically staged as ypTisN0. Postoperatively, the patient received 4 cycles of XELOX chemotherapy plus nivolumab, followed by consolidative radiotherapy synchronized with capecitabine and nivolumab, and subsequent maintenance therapy with capecitabine and nivolumab until sustained no evidence of disease (NED) was confirmed in January 2023. Regular surveillance, including the latest contrast-enhanced CT in May 2025, showed no recurrence or metastasis, with progression-free survival (PFS) exceeding 5 years. This exceptional and sustained response may be attributed to the synergistic effect of TMB-H and POLD1 mutation, which enhance neoantigen generation and sensitize tumors to immunotherapy. This case highlights the potential of biomarker-driven chemo-immunotherapy combined with MDT-guided multimodal treatment (surgery + adjuvant therapy + consolidative radiotherapy) to achieve curative intent in patients with metastatic GMC, providing valuable insights for personalized treatment strategies in this poor-prognosis population.

Tumor-associated macrophages (TAMs) are central regulators of the metabolic and immunological landscape of solid tumors and are increasingly recognized as key determinants of cancer-cell susceptibility to ferroptosis. Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation, is tightly shaped by metabolic cues within the tumor microenvironment (TME). TAMs, through their remarkable metabolic plasticity, modulate iron flux, redox balance, polyunsaturated fatty-acid (PUFA) availability, and glutathione-dependent antioxidant pathways, each of which directly influences ferroptotic vulnerability in neighboring tumor cells. In this review, we synthesize current evidence linking TAM polarization states to the regulation of ferroptosis-related processes, including lipid remodeling, cystokine metabolism, reactive oxygen species (ROS) buffering, and immunometabolic signaling. We further discuss how TAM-derived cytokines, lipid mediators, and iron-handling proteins orchestrate a microenvironment that either promotes or restrains ferroptotic cell death. Finally, we highlight emerging therapeutic strategies aimed at rewiring TAM metabolism or exploiting ferroptosis to overcome immune suppression and therapy resistance. By integrating immunological and metabolic dimensions, this review provides a framework for understanding TAM-ferroptosis crosstalk and its implications for precision immunotherapy in cancer.

Esophageal squamous cell carcinoma (ESCC) remains a major malignancy globally, and long-term survival outcomes remain poor despite advances in multimodal treatment strategies. Neoadjuvant therapy (NAT) has become the standard of care for resectable ESCC; however, substantial interpatient heterogeneity in treatment response persists. Defining malignant cell-intrinsic molecular determinants linked to NAT response is essential for improving prognostic stratification and informing individualized therapeutic decision-making.

To investigate transcriptional alterations in malignant epithelial cells, we analyzed scRNA-seq datasets obtained from ESCC patients both before and after NAT. Overlapping molecular features were identified by integrating differentially expressed genes from pre- and post-treatment malignant cells with bulk RNA-seq data from TCGA and GEO cohorts. Functional enrichment analyses, pseudotime trajectory reconstruction, and transcription factor regulatory network assessments were subsequently performed. Candidate prognostic genes were initially screened through univariate Cox analysis, followed by the development of the NTAMPS model using LASSO-Cox regression. Its prognostic performance was validated in the TCGA-ESCA and GSE53624 cohorts, and clinical applicability was further examined using a nomogram, calibration curves, and decision curve analysis. Immune-related associations, immunotherapy response prediction (IMvigor210 and GSE78220), and drug sensitivity profiling were also conducted. DUXAP8, which carried the largest coefficient in the NTAMPS, was selected for further validation through both in vivo and in vitro assays, including qRT-PCR and evaluations of cell proliferation, migration, invasion, and colony formation.

Malignant epithelial cells exhibited pronounced transcriptional remodeling after NAT, characterized by enrichment of pathways related to the cell cycle, DNA replication, and epithelial-mesenchymal transition. Cell-cell communication analysis revealed substantial reorganization of the MIF signaling pathway, including increased interactions of MIF-ACKR3 and MIF-(CD74+CXCR4/CD44), with fibroblasts acting as major signal senders and macrophages serving as primary receivers. Twenty-one prognosis-related genes were identified, and a ten-gene NTAMPS demonstrated strong prognostic performance. Both NTAMPS and clinical stage emerged as independent prognostic factors and were integrated into a nomogram with favorable calibration and decision curve characteristics. A high NTAMPS was associated with an immunosuppressive microenvironment, reduced predicted response to immunotherapy, and distinct drug sensitivity patterns. DUXAP8, the top positive risk gene within NTAMPS, was highly expressed in ESCC tissues and cell lines, and its silencing suppressed cell proliferation, migration, invasion, and clonogenic potential.

This study establishes NTAMPS as a novel malignant cell-derived prognostic signature for ESCC by integrating single-cell and bulk transcriptomic data. NTAMPS enables effective prognostic stratification, predicts potential immunotherapy benefit, and highlights therapeutic vulnerabilities. DUXAP8 was further identified as a candidate molecular driver that may improve ESCC management in the context of neoadjuvant therapy.

Several PD-1 inhibitors used in first-line treatment of advanced non-squamous non-small cell lung cancer in China, including sintilimab, toripalimab and camrelizumab, have demonstrated significant survival benefits in phase III trials. However, their comparative cost-effectiveness within the Chinese national medical insurance system remains unclear.

A Markov model with progression-free, progressive disease and death states was developed from the Chinese national medical insurance system payer perspective. Clinical efficacy inputs were obtained from three China-based phase III randomized trials. Individual patient data were reconstructed from published Kaplan-Meier curves using the Guyot method, and parametric survival models were fitted for extrapolation. Costs included drug acquisition, administration, adverse event management and post-progression therapy. Outcomes were total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were conducted.

Sintilimab incurred the lowest cost (230,813 CNY) and generated 1.1 QALYs. Toripalimab yielded the same QALYs at a higher cost and was strictly dominated. Camrelizumab produced the highest QALYs (1.2) at a total cost of 253,056 CNY. Compared with sintilimab, camrelizumab had an ICER of 164,983 CNY/QALY, below the willingness-to-pay threshold of 287,247 CNY/QALY. Sensitivity analyses confirmed the robustness of these findings.

Among the three domestic PD-1 inhibitors evaluated, camrelizumab is the most cost-effective first-line treatment option for advanced non-squamous NSCLC in China.

Ischemic preconditioning of parathyroid glands (IPCP) is biologically plausible but clinical evidence is limited. In this single-center randomized trial (ChiCTR2000039788), we compared IPCP versus control during total thyroidectomy with central neck dissection.

A total of 135 patients with differentiated thyroid carcinoma were analyzed (IPCP, n = 67; control, n = 68). IPCP consists of three cycles of 60-second occlusion followed by 60-second reperfusion of the ipsilateral superior and inferior thyroid arteries. The baseline characteristics, postoperative hypoparathyroidism (hypoPTH) and hypocalcemia, early parathyroid function recovery (PFR), and surgical complications, were compared between groups.

The incidence of postoperative hypoPTH and protracted hypoPTH was not significantly different between the IPCP and control groups (50.8% vs 41.2%, p = 0.265; 6.0% vs 14.7%, p = 0.096). An exploratory analysis showed a higher rate of early PFR in the IPCP group (88.2% vs 64.3%; p = 0.025). The incidence of postoperative hypocalcemia was similar between groups (79.1% vs 82.4%; p = 0.632). Fewer inadvertent parathyroidectomy occurred in the IPCP group, though this difference was not statistically significant (4.5% vs 8.8%; p = 0.505). Other surgical complications were comparable.

IPCP did not reduce postoperative hypoPTH in this randomized trial. Earlier PFR is exploratory and warrants further investigation in adequately powered trials.

Emotional-approach coping (EAC), including emotional expression (EE) and emotional processing (EP), may impact stress and quality of life (QOL) in cancer populations, with some evidence that EAC effects vary by sex.

Men (n = 85) and women (n = 63) with renal cell carcinoma (RCC) completed the EAC Scale, Perceived Stress Scale (PSS), and 36-item Medical Outcomes Study Short Form Survey (SF-36) physical component scale (PCS) and mental component scale (MCS) at study entry and 10 months later. The PROCESS macro (model 7) was used to examine the indirect effect of baseline EAC (EE, EP) on 10-month QOL (PCS, MCS) via baseline PSS, with sex as a moderator of the association between EAC and PSS (i.e., four models of moderated mediation).

Bootstrap estimates of indirect effects revealed significant moderated mediation, such that, for female participants, greater EE at study entry was associated with lower PSS, which in turn was associated with higher PCS and MCS 10 months later; whereas for males, EE was not associated with PSS and was not indirectly associated with physical and mental health-related QOL via PSS. Models examining the indirect effects of EP on QOL via PSS were nonsignificant for male and female participants.

EE is an important correlate of perceived stress for females but not males with RCC. Perceived stress early in treatment has a robust association with subsequent health-related QOL. Interventions aimed at supporting EE for females with RCC may have long-term QOL benefits.

Toxoplasma gondii (T. gondii) is a ubiquitous protozoan parasite capable of establishing lifelong latent infections in the central nervous system. Previous epidemiological studies have suggested a potential association between T. gondii infection and an increased risk of brain cancer, but the causal relationship remains unclear.

We conducted a bidirectional Mendelian randomization (MR) study to assess the causal relationship between T. gondii infection and brain tumor risk. Genetic instruments for T. gondii seropositivity were derived from a genome-wide association study (GWAS) in the UK Biobank, while genetic data for brain tumors were obtained from the FinnGen R12 dataset. Standard MR methods, including inverse-variance weighted (IVW), weighted median, and MR-Egger, were applied to infer causality, with generalized summary Mendelian randomization (GSMR) used for further validation. Sensitivity analyses, including heterogeneity and pleiotropy assessments, were performed to ensure robustness. Additionally, reverse MR analyses were conducted to evaluate whether brain tumors influence genetic liability to T. gondii seropositivity.

Our MR analyses found no evidence of a causal relationship between genetic liability to T. gondii seropositivity, as indicated by P22 and SAG1 antibody levels, and the risk of brain tumors. Across all tumor subtypes, IVW, weighted median, MR-Egger, and GSMR analyses consistently yielded non-significant results. However, reverse MR analysis suggested that genetic liability to malignant brain tumors is associated with increased odds of T. gondii seropositivity. For P22, a strong association was observed across methods (IVW: OR = 1.234, p = 0.004; GSMR: OR = 1.228, p = 0.006). In contrast, for SAG1 the evidence was weaker, with IVW indicating a suggestive association (OR = 1.094, p = 0.048) and GSMR showing a borderline association (OR = 1.088, p = 0.052). Sensitivity analyses confirmed the robustness of these findings, with no evidence of heterogeneity or pleiotropy. No significant associations were observed for meningioma, glioblastoma, or benign brain tumors.

Our study provides no evidence for a causal relationship between genetic liability to T. gondii seropositivity and brain tumor risk. However, reverse MR suggests that genetic liability to malignant brain tumors may be associated with increased odds of T. gondii infection.

Breast cancer survivors often face persistent physical and emotional challenges. Evidence suggests that physical exercise and group psychological interventions can improve well-being and illness adjustment. This pilot study examined the effectiveness of a combined intervention delivered in a natural environment. Sixty female breast cancer survivors (Mage = 51.0; SD = 5.5) participated in a 1-week program consisting of daily sailing lessons and group psychological sessions designed to address cancer-related issues. Assessments were conducted 1 week before and 1 week after the intervention using the Functional Assessment of Cancer Therapy-Breast (FACT-B) to assess quality of life and the State-Trait Anxiety Inventory. Linear mixed-effects models tested changes over time in quality of life and anxiety and whether previous psychotherapy or physical activity influenced these outcomes. FACT-B total scores significantly improved over time (P = 0.004), with gains in physical well-being (P < 0.001), emotional well-being (P < 0.001), and breast cancer-specific concerns (P = 0.018). No changes over time were observed in social or functional well-being. Anxiety levels remained moderate and stable (P = 0.250). Previous psychotherapy and physical activity did not significantly influence changes in quality of life or anxiety. A short-term group intervention combining sailing lessons and psychological sessions in a natural environment may enhance quality of life in breast cancer survivors, particularly in physical and emotional domains. These findings suggest that integrative approaches addressing both physical and psychological health are feasible and warrant further investigation in larger controlled studies.

Altered glymphatic function is observed for many neurological diseases. Glioma, one of the most common brain cancers, is known to have altered fluid dynamics in terms of edema and blood-brain barrier breakdown, both features potentially impacting the glymphatic function. To study glioma and its fluid dynamics, we propose a flexible mathematical model, including the tumor, the peri-tumoral edema and the healthy tissue. From a mechanical point of view, we consider the brain as a multicompartment porous medium and model both the fluid movement and the clearance of solutes within the brain. Our results indicate that the impairment of the glymphatic system due to glioma growth is two-fold. First, edema resulting from the leakage of fluid at the blood-brain barrier and/or the occlusion of the interstitial fluid exit routes (notably the perivascular spaces) due to migratory tumor cells result in a slight localized increase of pressure, consequently impairing negatively glymphatic clearance. Second, local changes of porosity (i.e. the volume fraction of certain compartments such as perivascular or extracellular spaces), result in a disruption of the transport of solutes in the brain. Our results indicate that an effect similar to the enhanced permeability and retention is obtained using biologically relevant changes of parameter values of our model. Our mathematical model is the first step towards a digital twin for drug or contrast product delivery within the cerebro-spinal fluid directly (e.g. from intrathecal injection) for patients suffering from gliomas.