Significant progress has been made in understanding the complex immune evasion mechanisms of triple-negative breast cancer (TNBC), paving the way for more effective immunotherapies. This review highlights key advances in elucidating the molecular basis of TNBC immune escape, including aberrant immune checkpoint expression, metabolic reprogramming, epigenetic regulation, immune evasion by associated cellular components, and clinical trials of emerging immunotherapies. Specifically, overexpression of immune checkpoint inhibitors such as PD-L1 on TNBC cells and within the tumor microenvironment (TME) plays a critical role in suppressing antitumor immunity. Secondly, TNBC cells evade immune surveillance through metabolic reprogramming. For instance, upregulated glutamine metabolism supports tumor growth and modulates the TME toward immunosuppression by limiting nutrient availability to immune cells. Competitive consumption of amino acids such as tryptophan and arginine further compromises immune cell function, promoting immune escape. Epigenetic modifications, including DNA methylation and histone modifications, are increasingly recognized as key contributors to immune evasion in TNBC. These mechanisms can silence genes involved in antigen presentation and immune activation while promoting the expression of immunosuppressive factors. Long non-coding RNAs (lncRNAs) have been identified as central regulators of immune evasion in TNBC, offering new therapeutic targets for intervention. Moreover, TNBC actively shapes its microenvironment to establish immunosuppression, including recruitment of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2-polarized macrophages, which collectively inhibit effector T cell function. Building on these mechanistic insights, this review also integrates findings from clinical trials evaluating next-generation immunotherapies, including bispecific antibodies targeting PD-1/CTLA-4, LAG-3 inhibitors, and CD47-SIRPα blockers, as well as potential biomarkers. These novel combination strategies aim to overcome resistance to single-agent checkpoint inhibitors, while research explores monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates (ADCs) within biomarker-driven personalized treatment frameworks. The ultimate goal is to improve survival and quality of life for TNBC patients through tailored immunotherapies.

Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) and antitumor immunity synchronously urgently needed. Here, the authors developed a nanoscale metal–organic framework (MOF, named TZM) by co‐doping high‐atomic elements Ta and Zr as metal nodes and porphyrinic molecules (tetrakis(4‐carboxyphenyl)porphyrin (TCPP)) as a photosensitizing ligand. Given the 3D arrays of ultra‐small heavy metals, porous TZM serves as an efficient attenuator absorbing X‐ray energy and sensitizing hydroxyl radical generation for RT. Ta–Zr co‐doping narrowed the highest occupied molecular orbital‐lowest unoccupied molecular orbital (HOMO–LUMO) energy gap and exhibited close energy levels between the singlet and triplet photoexcited states, facilitating TZM transfer energy to the photosensitizer TCPP to sensitize singlet oxygen (¹O₂) generation for radiodynamic therapy (RDT). The sensitized RT–RDT effects of TZM elicit a robust antitumor immune response by inducing immunogenic cell death, promoting dendritic cell maturation, and upregulating programmed cell death protein 1 (PD‐L1) expression via the cGAS–STING pathway. Furthermore, a combination of TZM, X‐ray, and anti‐PD‐L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma.

Background: To retrospectively analyze whether primary tumor volume and primary nodal volume could be considered independent prognostic factors for nasopharyngeal carcinoma treated with intensity-modulated radiation therapy. Methods: Three hundred sixty-three consecutive nasopharyngeal carcinoma (NPC) patients who were stage I-IVa+b and treated with intensity-modulated radiotherapy (IMRT) in our center from October 2003 to October 2005 were analyzed retrospectively. The predictive ability of gender, age, T and N stage, combined chemotherapy, primary tumor and nodal volume for the 5-year local control (LC), distant-metastasis free survival (DMFS) and overall survival (OS) rate were investigated. Primary tumor and nodal volume were measured based on registration of magnetic resonance imaging (MRI) with contrast-enhanced computed tomography (CT) images. The Kaplan–Meier method was used for survival analysis, the log-rank test was used for univariate analyses and the Cox proportional hazard model was used for multivariate prognostic analyses. Results: The mean value of primary tumor and nodal volume were 31.5 ml and 9.7 ml. The primary tumor and nodal volume were respectively divided into four groups for analysis (primary tumor volume: TV1≤20 ml, 20<TV2≤30 ml, 3040 ml; primay nodal volume: NV1≤5 ml, 5<NV2≤10 ml, 1020 ml). In univariate analysis, the 5-year LC and DMFS rate for TV4 was significantly decreased compared to the other groups (LC: p40 ml was an adverse prognostic factor for the 5-year local regional control (LRC) rate (RR 2.454, p=0.002). Primary nodal volume had no statistical significance in predicting 5-year LRC, DMFS and OS rate in multivariate analysis. Conclusions: Primary tumor volume could predict LRC rate of NPC patients, and the primary tumor volume of 40 ml may be the cut-off. Primary nodal volume may have predictive significance, but more data are needed. These factors should be considered in the TNM staging system of NPC for better estimates of prognosis.

Graphene with unique physical and chemical properties has shown various potential applications in biomedicine. In this study, a fast, facile and mass production method was reported to obtain stable and disperse polyethylene glycol (PEG) modified nanographene (NGO-PEG, 20–40 nm) by covalent functionalization with a linear chain PEG. X-ray photoelectron spectroscopy and UV/Vis indicated the successful preparation of NGO-PEG. Atomic force microscopy was used to show the structure and size of GO and NGO-PEG. The branched polyethylenimine (BPEI) modified NGO-PEG (NGO-PEG-BPEI) was strategically designed and prepared as the targeting drug delivery system to achieve higher specificity. The photosensitizer molecule Chlorin e6 (Ce6) was loaded onto NGO-PEG and NGO-PEG-BPEI via π–π stacking and hydrophobic interactions. The obtained NGO-PEG-Ce6 and NGO-PEG-BPEI-Ce6 show excellent photodynamic efficacy compared to free Ce6 because of the significantly enhanced intracellular delivery of Ce6. The NGO-PEG-BPEI-Ce6 offers a remarkably improved photodynamic efficacy. The drug loading capability, cell uptake, intracellular localization and ROS-producing ability were discussed to explain why NGO-PEG-BPEI-Ce6 had a higher photodynamic efficacy than free Ce6 and NGO-PEG-Ce6. Our study highlights a green route to synthesize stable and disperse NGO-PEG, and identifies a role for NGO-PEG-BPEI as a carrier to target lysosomes to improve the efficacy of photodynamic therapy.

Purpose: The near-infrared fluorescent dye indocyanine green (ICG) has shown great potential in the photodynamic therapy (PDT) and photothermal therapy (PTT) of cancer. However, its disadvantages of instability in aqueous solution, short half-life, and non-targeting accumulation limit the effectiveness of ICG PDT/PTT. To overcome the disadvantages of ICG in tumor treatment, we designed PEGylated-human serum albumin (PHSA)-ICG-TAT. In this nanoparticle, PEG4000, the HSA package, and nuclear targeting peptide TAT (human immunodeficiency virus 1 [HIV-1]-transactivator protein) were used to improve the water solubility of ICG, prolong the life span of ICG in vivo, and target the nuclei of tumor cells, respectively. Methods: The PHSA-ICG-TAT was characterized in terms of morphology and size, ultraviolet spectrum, dispersion stability, singlet oxygen and cellular uptake, and colocalization using transmission electron microscopy and dynamic light scattering, and fluorescence assay, respectively. Subsequently, the anti-tumor effect of PHSA-ICG-TAT was investigated via in vitro and in vivo experiments, including cell viability, apoptosis, comet assays, histopathology, and inhibition curves. Results: The designed ICG-loaded nanoparticle had a higher cell uptake rate and stronger PDT/PTT effect than free ICG. The metabolism of PHSA-ICG-TAT in normal mice revealed that there was no perceptible toxicity. In vivo imaging of mice showed that PHSA-ICG-TAT had a good targeting effect on tumors. PHSA-ICG-TAT was used for the phototherapy of tumors, and significantly suppressed the tumor growth. The tumor tissue sections showed that the cell gap and morphology of the tumor tissue had been obviously altered after treatment with PHSA-ICG-TAT. Conclusion: These results indicate that the PHSA-ICG-TAT had a significant therapeutic effect against tumors.