The ESTRO/EORTC classification categorizes oligometastatic disease (OMD) into de-novo, repeat, and induced OMD based on prior disease history and treatment status. However, its prognostic relevance in lung cancer patients treated with stereotactic ablative radiotherapy (SABR) remains incompletely characterized in real-world settings. This study evaluated the ESTRO/EORTC classification and two simplified binary stratification approaches derived from its decision framework. This single-center retrospective study included 648 lung cancer patients with 1–5 metastases treated with SABR between 2015 and 2021. Patients were categorized according to the ESTRO/EORTC classification. Two simplified binary stratification approaches derived from the ESTRO/EORTC decision framework were additionally explored: (1) a history-based approach distinguishing patients with prior polymetastatic disease from those without, and (2) a therapy-dependent progression approach distinguishing oligometastatic progression during active systemic therapy from other OMD states. Survival outcomes were analyzed using Kaplan-Meier and Cox regression, and prognostic discrimination was assessed using Harrell’s C-index. With a median follow-up of 54.5 months, 325 deaths and 552 progression events were observed. Induced OMD was associated with significantly worse outcomes compared with de-novo OMD (OS: 35.7 vs. 68.9 months; PFS: 8.6 vs. 15.5 months; both p < 0.001) and repeat OMD (OS: 35.7 vs. 60.2 months; PFS: 8.6 vs. 14.4 months; both p < 0.001). No significant differences were observed between de-novo and repeat OMD. The therapy-dependent progression stratification approach demonstrated distinct survival separation (median OS 34.4 vs. 86.4 months; PFS 8.4 vs. 16.4 months; both p < 0.001), although the difference in discriminatory performance was modest (C-index 0.596 for OS) compared with the ESTRO/EORTC classification (0.565) and the history-based approach (0.563). Differences in discriminatory performance were modest and not statistically significant after multiple-testing correction and bootstrap resampling. The ESTRO/EORTC classification is associated with survival outcomes in lung cancer patients with OMD treated with SABR, with induced OMD conferring the poorest prognosis. Simplified binary stratification approaches derived from this framework may provide a pragmatic and clinically accessible approach for risk stratification. These approaches should be considered complementary to, rather than replacements for, the full ESTRO/EORTC classification. Prospective validation is warranted.

Background: In neoadjuvant chemoradiotherapy (NCRT), only 1/3 of patients with esophageal squamous cell carcinoma (ESCC) achieve pathologic complete response (pCR). Here, we aimed to depict the biological landscape of ESCC with different responses to NCRT and identify biomarkers to facilitate clinical decisionmaking. Methods: Tumor specimens before NCRT were obtained for whole exome sequencing (WES), RNA sequencing, and data-independent acquisition (DIA) mass spectrometry. Genomic data were analyzed for significantly mutated genes (SMGs), copy number alterations, microsatellite instability (MSI), tumor mutation burden (TMB), and mutational signatures. Transcriptomic and proteomic data were used to examine differentially activated pathways. Gene set enrichment analysis (GSEA) and ActivePathways were used for single omics and joint multiomics analyses, respectively. Treatment-resistance biomarkers were identified and confirmed in a separate cohort using immunohistochemistry (IHC). Results: FBXW7 mutation (Fisher's exact test, P=0.03) and 9p21.3 cytoband loss (q-value =0.001) are the significant genetic variations in the pCR group. Combined transcriptomic and proteomic analyses revealed that the type I interferon signaling pathways and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathways were enriched in non-pCR tumors. A biomarker panel of 12 proteins predictive of nonpCR tumors was identified, 10 of which were verified using multiplex IHC (mIHC) in an independent cohort. Conclusions: We described the multiomic biological characteristics of ESCC with distinct responses to NCRT and proposed a panel of proteins as predictive biomarkers for non-pCR patients.

Background:Non-small cell lung cancer (NSCLC) patients undergoing postoperative radiotherapy (PORT) after lung resection present a unique challenge due to anatomical changes and reduced baseline lung capacity. Standard dosimetric constraints established for intact lungs may not be applicable. This study aims to identify key risk factors and develop a model for predicting grade ≥ 2 (G2+) radiation pneumonitis (RP) through a secondary analysis of a prospectively collected cohort of NSCLC patients treated with PORT following lobectomy or sleeve resection. Methods:Data from patients with completely resected stage T1-3N2M0 (7th Edition) NSCLC receiving PORT were drawn from two prospective, multicenter, randomized trials (NCT02977169, NCT02974426) initiated in 2016. The endpoint was G2+ RP (Common Terminology Criteria for Adverse Events v5.0) within one year after radiotherapy. Least absolute shrinkage and selection operator (LASSO) regression, univariable and multivariable Cox proportional hazards models were utilized to identify contributing parameters. A nomogram for G2+ RP was developed and validated using the concordance index (C-index), time-dependent C-index curves, calibration curves, and decision curve analysis. Results:Of the 178 eligible patients, 21 developed G2+ RP, with a 12-month cumulative incidence of 11.8%. Age ≥67 years, the percentage of lung volume exceeding 13 Gy (V13) of the lung ≥25%, and the absolute lung volume spared from a 5 Gy dose (VS5) <1,230 cc were key risk factors for G2+ RP. The predictive model integrating age, V13, and VS5 achieved the bootstrap-corrected C-index of 0.757. Additionally, patients could be further stratified into low-risk (0 or 1 risk factor) and high-risk (2 or 3 risk factors) groups, with cumulative G2+ RP incidences of 6.6% and 29.3%, respectively (P<0.0001). Exploratory V13 thresholds were also proposed to help limit the incidence of G2+ RP. Conclusions:The combination of age (≥67 years), V13 (≥25%), and VS5 (<1,230 cc) effectively estimated the risk of G2+ RP in NSCLC patients receiving PORT after lung resection. Our findings underscore the importance of preserving a sufficient volume of normal lung tissue from low-dose exposure to ensure safety in patients with reduced lung reserve. Given the relatively limited number of events in our analysis, these findings are exploratory and require validation in larger, prospective cohorts.

Abstract: Background: Prostate cancer progression is influenced by the tumor microenvironment. Bone marrow mesenchymal stem cells (BMSCs) can modulate tumor behavior, but the role of their lncRNA PVT1 is unclear. Objective: To investigate whether lncRNA PVT1 in BMSCs regulates the malignant phenotype of prostate cancer cells through miR-122 and elucidate its mechanism of action in the tumor microenvironment. Method: Rat BMSCs were isolated and cultured and a Transwell co-culture system was established with human prostate cancer cell lines (PC-3). RT-qPCR was used to detect the expression of PVT1 and miR-122 in BMSCs and cancer cells. PVT1 was overexpressed and knocked down in BMSCs to observe its effects on cancer cell proliferation (CCK-8), apoptosis (flow cytometry) and cell cycle (PI staining) in the co-culture system. The targeting relationship between PVT1 and miR-122 was validated using a dual-luciferase reporter assay. Rescue experiments were performed by simultaneously manipulating PVT1 and miR-122 in BMSCs. Results: In prostate cancer patient tissues and cell lines, PVT1 expression was downregulated while miR-122 expression was upregulated. In the co-culture system, overexpression of PVT1 in BMSCs significantly inhibited cancer cell proliferation, arrested the cell cycle at the G0/G1 phase and promoted apoptosis. Conversely, knockdown of PVT1 in BMSCs promoted the malignant phenotype of cancer cells. Mechanistically, PVT1 directly targeted and negatively regulated miR-122. Overexpression of miR-122 reversed the inhibitory effect of PVT1 overexpression in BMSCs on cancer cells. Conclusion: BMSCs exert a tumor-suppressive effect in the prostate cancer microenvironment through the PVT1/miR-122 axis, which may serve as a novel therapeutic target for prostate cancer.

4086 Background: Definitive concurrent chemoradiotherapy (dCRT) is the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). However, when dCRT fails, salvage esophagectomy is technically challenging. Moreover, optimizing patient selection for dCRT remains an unresolved concern. We propose a stratified screening strategy by incorporating induction immunochemotherapy, aiming to identify suitable candidates for organ-sparing dCRT and timely surgical treatment. Methods: This prospective interventional phase II study (SCENIC, ChiCTR2200057732) enrolled patients with clinical stage T 2-4 N any M0 (AJCC TNM 8th) resectable CESCC. Eligible participants received induction therapy (IT) of intravenous PD-1 inhibitor tislelizumab (200mg, day 1) plus nab-paclitaxel (100 mg/m 2 , day 1,8,15) and carboplatin (area under curve of 5 mg/mL/min, day 1), administered over two 3-week cycles. Four weeks after IT, treatment response was evaluated via endoscopy and PET-CT. Patients were then divided into 3 groups: remarkable response (RR); limited partial response (LPR); and poor response (POR). RR patients received dCRT, while LPR and POR patients underwent radical surgery. Tislelizumab was maintained after dCRT in RR patients, and postoperative adjuvant therapy was dependent on the patient’s condition, including chemotherapy, radiotherapy, immunotherapy, or follow-up. The primary endpoint is 2-year event-free survival (EFS). Results: From Jul 2022 to Sep 2024, 42 patients were enrolled, with 40 completing two-cycle IT and response evaluation. Post-IT responses were RR in 62.5% (25/40), LPR in 25.0% (10/40), and POR in 12.5% (5/40). All RR patients received subsequent dCRT. In 11 non-RR patients,7 underwent total phryngo-laryngo-esophagectomy(TPLE), 4 received dCRT. Overall, 40 patients (96.0%) had any-grade treatment-related adverse events with leukocytopenia being most prevalent. 5 patients (12.5%) had adverse events of grade 3 or worse. With a median follow-up of 22.3 months (range, 4.5-40.9 months), 2-years EFS rate and overall survival (OS) rate in ITT population was 60.9% and 76.6%. 2-years EFS rate and OS rate in RR group and non-RR group is 78.8% vs 28.0%(p = 0.0011) and 84.8% vs 70.1%(p = 0.0703), respectively. Conclusions: The 2-year survival of RR patients with dCRT followed by IT appears promising compared to historical data. This stratified strategy of induction immunochemotherapy is effective in identifying candidates suitable for dCRT in patients with resectable CESCC. Clinical trial information: ChiCTR2200057732.

Prognostic nutritional index (PNI) has been widely investigated as a predictor of outcomes in patients with cancer; however, a comprehensive synthesis evaluating the breadth, methodological quality, and certainty of this evidence is lacking. We aimed to systematically review and critically appraise existing meta-analyses on the association between PNI and cancer prognostic outcomes. We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from database inception through 28 February, 2025. Methodological quality of included systematic reviews and meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. The protocol was registered prospectively on the International Platform of Registered Systematic Review and Meta-analysis Protocols platform (INPLASY2025110096). A total of 64 systematic reviews and meta-analyses, comprising 265 quantitative syntheses, were included. Of these, 224 (84.5%) reported statistically significant quantitative syntheses (P < 0.05) under random-effects models. AMSTAR assessment classified 44 (68.8%) systematic reviews and meta-analyses as high quality. GRADE evaluation indicated that 121 (45.7%) quantitative syntheses were supported by high-certainty evidence. Elevated PNI was consistently associated with improved overall survival (OS) across both pan-cancer and cancer-specific analyses. In pan-cancer populations, higher PNI was significantly associated with longer OS, prolonged progression-free survival, and higher objective response rates. Significant prognostic benefits of elevated PNI for OS were also observed in specific malignancies, including pancreatic cancer, gastric cancer, advanced-stage lung cancer, and glioma. Although a higher PNI is robustly associated with favorable prognostic outcomes in diverse cancers, marked heterogeneity in PNI cutoff values across studies underscores the urgent need for standardized, population-specific thresholds validated through prospective diagnostic accuracy studies.

Background and purpose: We aimed to assess the benefits of postoperative radiotherapy (PORT) in completely resected patients with pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) with a high risk of locoregional recurrence (LRR). Materials and methods: A prospective, randomized trial was conducted starting in July 2016 to explore the optimal timing of PORT in high-LRR-risk patients with completely resected IIIA(N2) NSCLC (NCT02974426). Patients were identified as high-LRR-risk patients via the prognostic index (PI) model and were randomly assigned to PORT-first or PORT-last treatment. To evaluate PORT for high-LRR-risk patients, all patients in this trial constituted the PORT cohort, whereas high-LRR-risk patients without PORT were selected from a retrospective cohort as the non-PORT cohort. Propensity score-matched (PSM) analyses were conducted to compare overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Results: Between 2016 and 2022, 132 patients were included in the trial, with a median follow-up of 49.3 months. The 3-year OS rate was 83.2 %, and the 3-year DFS rate was 35.0 %. Among these patients, 122 patients (92 %) received planned PORT. For 132 intention-to-treat patients, PSM analysis with the non-PORT cohort (n = 307) resulted in 130 matched pairs. The results revealed that PORT improved LRFS (3-year LRFS, 77.6 % vs. 57.3 %; p = 0.00014), DFS (3-year DFS, 35.2 % vs. 28.6 %; p = 0.038), and OS (3-year OS, 83.0 % vs. 60.7 %; p = 0.00017), with no difference in DMFS (p = 0.17). Conclusion: PORT could increase local control, DFS, and OS in high-LRR-risk patients with completely resected IIIA(N2) NSCLC. Future research should utilize multidimensional data to pinpoint more precise subgroups benefiting from PORT, with prospective trials validating these findings.

Supplemantary Video 2, LLC1 cells under monoculture

With the advancement of immunotherapy, neoadjuvant immunochemotherapy has emerged as an effective approach for treating locally advanced esophageal squamous cell carcinoma (LA‐ESCC). However, whether radiotherapy can serve as a reliable organ‐preserving alternative following induction immunochemotherapy (IICT), and which patient subgroups benefit most, remains uncertain. In this retrospective study, 388 patients with LA‐ESCC were analyzed, including 299 who underwent surgery and 89 who received radiotherapy after IICT. Responses to immunochemotherapy were classified as major pathologic response (MPR) or non‐MPR based on pathologic examination for surgical patients and a previously developed MPR predictive model for radiotherapy patients. Survival outcomes were assessed using the Kaplan–Meier method, while prognostic factors were evaluated through Cox regression analyses. Propensity score matching (PSM) was used to minimize confounding factors. Surgery was associated with better progression‐free survival (PFS) compared to radiotherapy ( p = 0.002 before PSM; p = 0.017 after PSM), but no significant difference in overall survival (OS) was observed ( p = 0.144 before PSM; p = 0.241 after PSM). Among MPR patients, radiotherapy achieved PFS and OS outcomes similar to surgery (PFS: p = 0.136; OS: p = 0.255) after PSM. Failure patterns differed, with local or regional recurrence being more common in the radiotherapy group, while distant metastasis was prevalent in surgery patients. Major postoperative complications occurred in 9.36% of surgery patients, and 11.2% of radiotherapy patients had grade 3–4 adverse events. These findings indicate that radiotherapy could be a safe and effective organ‐preserving alternative for LA‐ESCC patients, especially those achieving MPR, offering more personalized and less invasive treatment options while maintaining quality of life.

To develop a deep learning (DL) model for predicting disease-free survival (DFS) in clinical stage I lung cancer patients who underwent surgical resection using pre-treatment CT images, and further validate it in patients receiving stereotactic body radiation therapy (SBRT). A retrospective cohort of 2489 clinical stage I non-small cell lung cancer (NSCLC) patients treated with operation (2015–2017) was enrolled to develop a DL-based DFS prediction model. Tumor features were extracted from CT images using a three-dimensional convolutional neural network. External validation was performed on 248 clinical stage I patients receiving SBRT from two hospitals. A clinical model was constructed by multivariable Cox regression for comparison. Model performance was evaluated with Harrell’s concordance index (C-index), which measures the model’s ability to correctly rank survival times by comparing all possible pairs of subjects. In the surgical cohort, the DL model effectively predicted DFS with a C-index of 0.85 (95

Supplemantary Video 1, LLC1 cells cocultured with NG2+ BMSCs

Supplemantary Video 4, LLC1 cells cocultured with NG2+ Ncadherin KO BMSCs

summarized excel file containing the quantitative raw data and processed values in the manuscript

BACKGROUND:Neoadjuvant immunochemotherapy has demonstrated promising efficacy in locally advanced esophageal squamous cell carcinoma (ESCC), yet the role of adjuvant therapy remains unclear. This study aimed to develop a pathologic classification scheme to distinguish postoperative outcomes and explore the potential benefit of adjuvant therapy. METHODS:This study retrospectively collected data on patients with locally advanced ESCC who underwent radical esophagectomy after neoadjuvant immunochemotherapy between 2019 and 2022. The primary outcome was recurrence-free survival (RFS), and secondary outcomes included recurrence patterns, overall survival, locoregional recurrence-free survival, and distant metastasis-free survival. The Kaplan-Meier method was used to plot survival curves, propensity score matching was used to match different groups, and Cox proportional hazards models identified factors affecting prognosis. RESULTS:Among 333 eligible patients, the overall pathologic complete response (pCR) rate was 25.8%. With a median follow-up of 23.8 months, the 1-year and 2-year RFS rates were 77.0% and 63.2%, respectively. Multivariable analysis identified ypN as the primary factor influencing RFS, while both ypN and MPR status were key determinants of recurrence patterns. A classification approach based on MPR and ypN status was developed to distinguish patient subgroups with different RFS and recurrence patterns. Patients with ypN0 had a favorable prognosis. In ypN+ patients, MPR was linked to more locoregional recurrences, while non-MPR cases showed mainly distant metastases. Among MPR ypN+ patients, adjuvant therapy was associated with improved RFS (hazard ratio, 0.38; 95% confidence interval, 0.15- 0.93; P = .028). CONCLUSIONS:The MPR-ypN-based classification distinguishes postoperative outcomes and suggests that MPR ypN+ patients may derive benefit from adjuvant therapy.

Supplementary figures and corresponding figure legends

Chronic kidney disease (CKD) is characterized by persistent inflammation and tubulointerstitial fibrosis leading to end‐stage renal disease. Transient receptor potential canonical 6 (TRPC6) channel inhibition mitigates tubular injury and renal fibrosis in murine models of unilateral ureteral obstruction (UUO) and 2‐month chronic post–ischemia‐reperfusion injury (2m post‐I/R). Through integrated analysis of single‐cell‐RNA‐sequencing (scRNA‐Seq) data from UUO mice treated with the selective TRPC6 inhibitor SH045, here the renoprotective cell composition and cell type‐specific transcriptional programs are defined. We explored translational aspects by conducting an in‐depth scRNA‐Seq analysis of kidney samples from patients with CKD. These results reveal global transcriptional shifts with a dramatic diversification of inflammatory cells, endothelial cells and fibroblasts. Notably, a distinct subpopulation of novel endothelial cells is delineated, which is termed ECRIN, that regulate inflammatory networks implicating VEGF and GAS signaling pathways. The data also indicates that inhibition of TRPC6 channels triggers a Prnp transcription factor regulatory network, which contributes to the alleviation of renal fibrosis. The key findings are supported at the protein level by immunofluorescence and western blot analysis. We observed similar patterns in the chronic 2m postI/R injury model. These findings provide novel insights into the potential therapeutic benefits of TRPC6 inhibition in CKD.

Plexiform neurofibromas (PNFs) are a prevalent and severe phenotype associated with NF1, characterized by a high teratogenic rate and potential for malignant transformation. The growth and recurrence of PNFs are attributed to aberrant proliferation and migration of Nf1-deficient Schwann cells. Protein tyrosine phosphatase receptor S (PTPRS) is believed to modulate cell migration and invasion by inhibiting the EMT process in NF1-derived malignant peripheral nerve sheath tumors. Nevertheless, the specific role of PTPRS in NF1-derived PNFs remains to be elucidated. The study utilized the GEO database and tissue microarray to illustrate a decrease in PTPRS expression in PNF tissues, linked to tumor recurrence. Furthermore, the down- and over-expression of PTPRS in Nf1-deficient Schwann cell lines resulted in the changes of cell migration and EMT processes. Additionally, RTK assay and WB showed that PTPRS knockdown can promote EGFR expression and phosphorylation. The restoration of EMT processes disrupted by alterations in PTPRS levels in Schwann cells can be achieved through EGFR knockdown and EGFR inhibitor. Moreover, high EGFR expression has been significantly correlated with poor prognosis. These findings underscore the potential role of PTPRS as a tumor suppressor in the recurrence of PNF via the regulation of EGFR-mediated EMT processes, suggesting potential targets for future clinical interventions.

Abstract Background After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10–12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. Discussion If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). Trial registration The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019).

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)(+) myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8(+) myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8(+) myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser(772) by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8(+) myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8(+)SIRT6(low) myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8(+) myCAFs is a promising approach to circumvent chemoresistance.

The hypoxic microenvironment within the tumor microenvironment of breast cancer imposes a challenge in overcoming chemotherapy resistance. In this investigation, we designed a novel strategy utilizing a light-controlled cascade targeting nanomedicine specifically tailored for enhanced immune therapy of breast cancer. Albumin nanoparticle was achieved by crosslinking, followed by loading TPZ and Ce6, and subsequent modification to enable selective binding with CD44 hyaluronic acid to form nanomedicine. Encouragingly, it was demonstrated the remarkable ability of the nanomedicine to effectively internalize into cellular entities, thereby inducing apoptosis in 4T1 cells efficiently in vitro when exposed to light irradiation. In vivo assessments showcased the exceptional aptitude of the nanomedicine not only for preferential accumulation within tumor tissues, but also for substantial suppression of tumor growth. Immune mechanisms have shown that nanomedicine treatment promoted the maturation of DCs in vivo, enhanced the proportion of CD8+ T cells in the spleen and tumor, and simultaneously upregulated the ratio of M1 macrophages favorable for anti-tumor effects. These outcomes collectively advance a fresh perspective for the clinical breast cancer therapy.