Abstract Background: Tumor-infiltrating lymphocytes (TIL) adoptive therapy has shown clinical efficacy for metastatic melanoma refractory to anti-PD-1 therapy. This phase I clinical trial evaluated the safety and efficacy of TILs (LM103) in advanced Chinese patients (pts) with melanoma, and explored correlative biomarkers. Methods: Pts with metastatic melanoma progressing on standard therapies, had both resectable and measurable tumors were eligible to be enrolled. Pts received a lymphodepletion regimen before the intravenous autologous LM103 infusion and then high dose IL-2 for 6 doses (200000IU/Kg, 1 dose per day) to support T cell survival and proliferation. Primary endpoint was safety; secondary endpoints included efficacy and translational analysis. Results: Fourteen pts (4 males; aged 26-70 yrs) were enrolled: 5 acral, 4 cutaneous, 4 mucosal, and 1 unknown primary. Infused autologous TIL contained 3.58-19.47x10^10 viable cells. The most frequent treatment-emergent adverse events (TEAEs) were myelosuppression (100%), fever (85.7%), rash (71.4%), and alopecia (71.4%). Grade 3-4 TEAEs included leukopenia (85.7%), neutropenia (78.6%), lymphopenia (78.6%), fever (71.4%), thrombocytopenia (57.1%), and anemia (28.6%). The ORR and DCR per RECIST v1.1 were 35.7% and 85.7%, respectively. With a median follow-up of 5.51 months, the median PFS and OS were 4.52 months (95% CI, 2.07 to 14.31) and 16.58 months (95% CI, 5.16 to NA), respectively. Immunofluorescence analysis and whole-exome sequencing for the baseline tumors did not reveal any significant difference in the infiltration of multiple immune cell populations and tumor mutation burden, respectively, between responders (Rs) and non-responders (NRs). T cell receptor-sequencing (TCR-seq), flow cytometry analysis and ELISA were performed for the TIL infusion products and the peripheral blood of patients at various time points before and after infusion. The frequency of shared T cell clones between TIL infusion products and post-infusion peripheral blood maintained >60% till 6 month after infusion, indicating that LM103 TILs persisted well in vivo. The frequencies of dominant T cell clones of infused TILs were higher in Rs than in NRs, implying a correlation between TILs persistence and clinical outcome. In addition, the IFN-γ level in the peripheral blood at Week 6 of NRs was significantly higher than that of Rs while other cytokine (such as TNF-α, IL-2, TGF-β1 etc) levels were similar between these two groups. Percentage of CD3+, CD4+ or CD8+ T cells in the peripheral blood was also not significantly different between R and NRs. Conclusion: LM103 TIL therapy demonstrated manageable safety and encouraging efficacy in treatment-refractory melanoma. Clinical response correlated with the persistence and expansion of infused TIL clones, instead of baseline tumour features. Trial registration number: CTR20233999. Citation Format: Chuanliang Cui, Li Zhou, Yan Kong, Xuan Wang, Yue Yang, Jiayong Liu, Zhichao Tan, Zhihong Chi, Lu Si, Bin Lian, Lili Mao, Hui Tian, Yuan Yuan, Yongming Xue, Jun Guo. Updated clinical efficacy and translational biomarker analysis of tumor infiltrating lymphocyte therapy (LM103) in metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB414.

BackgroundHepatocellular carcinoma (HCC) is a critical condition characterized by unchecked cellular growth in the liver, often leading to systemic inflammation and organ failure. Although its complex molecular mechanisms are not fully understood, the primary aim of this study is to enhance the timely and effective diagnosis and treatment of HCC by identifying key molecular targets and pathways.MethodsMicroarray datasets from the NCBI Gene Expression Omnibus were analyzed to identify differentially expressed genes (DEGs) in HCC patients compared with controls. Shared DEGs were subjected to functional enrichment analyses. Weighted gene coexpression network analysis (WGCNA) and single-cell sequencing were used to identify gene modules. Immune cell infiltration was assessed via single-sample gene set enrichment analysis (ssGSEA). In addition, a diagnostic model was constructed via various machine learning algorithms, validated via 10-fold cross-validation, and tested on external datasets.ResultsEight key genes significantly associated with HCC, primarily involved in immune and inflammatory responses, were identified. Enrichment analysis highlighted their roles in critical biological processes and pathways. Immune infiltration analysis revealed distinct immune profiles in HCC patients, differentiating them from healthy controls. A novel 8-gene diagnostic signature (ECM1, HAMP, MT1H, MT1F, CYP1A2, ASPM, CXCL14, and FCN3) demonstrated superior diagnostic performance over existing models, achieving an area under the curve (AUC) of 1.000 in training cohorts with robust validation in external datasets.ConclusionThe integration of machine learning with genomic data facilitated the development of a robust diagnostic model for HCC, emphasizing genes involved in immune responses. The identified genes and new diagnostic signatures offer valuable insights into the pathophysiology of HCC and hold potential for enhancing diagnostic strategies and patient management.

9537 Background: Homologous recombination deficiency (HRD) describes a tumor cell state characterized by impaired DNA double-strand break repair via the homologous recombination repair (HRR) pathway. Deficiencies in this pathway may serve as predictive biomarkers. However, the relevance of HRR gene mutations remains inadequately characterized in non-cutaneous melanoma. In this study, we aimed to delineate the mutational landscape of HRR genes in this population and evaluate their predictive implications for clinical management. Methods: We conducted a retrospective analysis of 932 patients with non-cutaneous melanoma treated at Beijing Cancer Hospital from January 2008 to January 2026. Tumor genomic profiling was performed using targeted next-generation sequencing with either an 81- (n=852) or a 425-gene (n=80) panel. Associations between HRR mutation status and survival outcomes were assessed using Kaplan-Meier survival estimates and Cox proportional hazards regression models. Results: HRR mutations were identified in 92 patients (9.9%), with the most frequent alterations occurring in ATM (3.5%), ARID1A (3.4%), BRCA2 (2.7%), and BRCA1 (1.8%). Within this HRR-mutated cohort, the primary subtypes were mucosal (44.6%) and acral (29.3%) melanoma. And the disease stages were distributed as follows: stage I, 31 patients (33.7%); stage II, 15 (16.3%); stage III, 22 (23.9%) and stage IV, 24 (25.0%). After a median follow-up of 63.7 months, the median overall survival (OS) was 57.5 months (95% CI: 43.4–71.7), with 1-, 2-, 3-, and 5-year OS rates of 92.1%, 84.9%, 74.7%, and 56.8%, respectively. Multivariate analysis confirmed age ≥65 years as an independent predictor of poorer overall survival (HR 2.7, 95% CI 1.3–5.4, P = 0.005), whereas ATM mutation emerged as a significant protective factor associated with a 68% reduction in mortality risk (HR 0.32, 95% CI 0.1–0.7, P = 0.007). Among 59 HRR-mutated patients who received first-line systemic therapy, 41 were treated with anti-PD-1-based regimens and 18 with non-PD-1-based regimens. In the 54 evaluable patients, median progression-free survival (PFS) was 9.0 months (95% CI: 3.8–14.2) and median OS was 55.0 months (95% CI: 39.0–71.0). The objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 61.1%. The DCR was 77.8% (21/27) in the mucosal subgroup versus 37.5% (6/16) in the acral subgroup with a statistically significant difference (P = 0.028). In a subgroup analysis, although not statistically significant, anti-PD-1-treated patients trended toward a longer median PFS compared with those not receiving anti-PD-1 therapy (15.0 vs. 6.0 months, P = 0.249). Conclusions: HRR mutations define a distinct molecular subset in non-cutaneous melanoma. ATM mutation serves as an important prognostic biomarker, and patients with HRR-mutated melanoma may derive survival benefit from anti-PD-1 immunotherapy.

Lung cancer has the highest incidence and mortality rates among all malignant tumors worldwide, with poor treatment outcomes and a high risk of postoperative recurrence. Currently, more than 50% of lung cancer cases are lung adenocarcinoma, which is characterized by early metastasis, recurrence, and therapeutic challenges. However, lung adenocarcinoma underlying nosogenesis mechanisms remain unclear. miRNAs are small non-coding RNAs that play crucial roles in regulating cell differentiation, proliferation, apoptosis, and other processes. They exert biological functions by suppressing the expression of target genes and have emerged as key players in cancer diagnosis, treatment, and prognosis evaluation. Numerous studies have shown that miR-542-3p is aberrantly expressed in various tumors and can either promote or inhibit the development and progression of multiple malignancies. This study aims to investigate the expression of miR-542-3p in lung adenocarcinoma and its effects on the biological behavior of lung adenocarcinoma cells, as well as to analyze the relationship between miR-542-3p, TTF1, and the MAPK pathway, with the goal of identifying novel therapeutic targets for lung adenocarcinoma. The results demonstrate that miR-542-3p is lower expressed in lung adenocarcinoma, where it directly regulates TTF1 expression and subsequently inhibits the MAPK signaling pathway indirectly via TTF1 downregulation, thereby reducing the proliferation, migration, and invasion capabilities of lung adenocarcinoma cells and suppressing tumor growth. This study is the first to reveal the critical role of the miR-542-3p/TTF1/MAPK regulatory axis in lung adenocarcinoma cell proliferation, migration, invasion, and tumor growth.

This study was aimed at determining the risk factors for postoperative dysphagia, a common complication, in patients with oral cavity and oropharyngeal cancers. PubMed, Embase, Web of Science Core Collection, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang, SinoMed, and Weipu were searched up to July 9, 2023, for cross-sectional, cohort, and case-control studies on postoperative dysphagia-associated factors in patients with oral cavity and oropharyngeal cancers. Two researchers independently screened the articles. Twenty-one studies involving 3352 patients with oral cavity and oropharyngeal cancers were included. The relationship between postoperative dysphagia and 22 factors was analyzed. Nine of these were considered as definite or possible risk factors, including age of ≥ 60 years (odds ratio [OR] = 3.161, 95

Background: Periampullary carcinoma (PAC) is a relatively rare but highly aggressive malignancy, posing challenges to the determination of the optimal therapeutic approach. The objective of this study was to clarify the potential of histopathological typing in guiding chemotherapy selection for patients with advanced PAC and to characterize the distinct molecular features, underlying functional changes, and regulatory mechanisms associated with the different subtypes. Methods: We conducted a retrospective analysis of clinical data from patients with advanced PAC admitted to the Oncology Department of Xijing Hospital between January 2015 and May 2022. These patients received first-line chemotherapy with either FOLFOX (folinic acid, fluorouracil, and oxaliplatin) or gemcitabine-based regimens. Certain patients were divided into the pathological typing group and the control group. The pathological typing group received subtype-specific chemotherapy regimens, while the control group received chemotherapy regimens based on the primary tumor site. We compared the median progression-free survival (PFS) and overall survival (OS) between the two groups. Using publicly available databases (GSE60980), we conducted differential gene screening, enrichment analysis, and immune cell infiltration assessment. A protein-protein interaction (PPI) network was constructed based on the differentially expressed genes, resulting in the identification of 60 node genes. Subsequently, a core gene selection using the least absolute shrinkage and selection operator (LASSO) regression machine learning algorithm was performed to identify the key genes specific to PAC-PB subtype. Results: The pathological typing group consisted of 46 patients, with 26 classified as the PB subtype and 20 as the IN subtype, while the control group comprised 40 patients. Compared to those in the control group, patients in the pathological typing group demonstrated significant improvements in overall response rate (20.5% vs. 12.9%; P=0.04), median PFS (8.1 vs. 5.4 months; P=0.04), and median OS (34 vs. 25.9 months; P=0.02). Multivariate Cox regression analysis revealed that pathological typing independently influenced PFS [hazard ratio (HR) =0.20, 95% confidence interval (CI): 0.10-0.44; P=0.009] and OS (HR =0.21, 95% CI: 0.17-0.71; P=0.02). Using a publicly available PAC cohort (GSE60980), we selected 154 differentially expressed genes, which were significantly enriched in signaling pathways related to the cell cycle, fibroblasts, and epithelial-mesenchymal transition. Analysis of immune cell infiltration indicated a significant increase in the abundance of fibroblast cells and a significant decrease in that of B cells and gamma delta T cells in the PAC-PB subtype. Furthermore, we identified core genes specific to the PAC-PB subtype and used them to construct a PAC-PB diagnostic model. Conclusions: Pathologic typing-guided individualized chemotherapy resulted in prolonged survival for patients with advanced PAC. The PB and IN subtypes of PAC exhibit distinct molecular regulatory mechanisms and immune infiltration microenvironments. These findings underscore the importance of considering subtype-specific factors in the development of a PAC-PB diagnostic model.

Background:Micropapillary (MP) pattern has been identified as a negative prognostic factor in patients with lung adenocarcinoma, but it has not been recognized as a high-risk factor for patients with stage IB lung adenocarcinoma treated with adjuvant chemotherapy. This multicenter cohort study aimed to evaluate the prognostic value of histological subtypes for stage I lung adenocarcinoma and to determine the relative survival benefit of adjuvant chemotherapy for subgroups based on MP pattern. Methods:This retrospective study included 412 patients with stage I lung adenocarcinoma [according the eighth edition of the tumor-node-metastasis (TNM) classification] with MP pattern who underwent complete surgical resection between January 2010 and December 2019. Patients were classified into 3 groups based on the proportion of MP component (10% and 50% as the threshold): MP component >50% (n=8), 10-50% (n=273) and <10% (n=131). Results:Among the 412 patients, the median age was 63 years, and 73.4% (113/154) patients with MP component ≥10% and 63.8% (51/80) of those with MP component <10% had epidermal growth factor receptor (EGFR) mutations. Patients with MP component >50% had a shorter overall survival (OS) compared with those with MP components of 10-50% [10-50% vs. >50%: hazard ratio (HR) =0.293, 95% confidence interval (CI): 0.083-1.027; P=0.052] or <10% (<10% vs. >50%: HR =0.214, 95% CI: 0.056-0.816; P=0.02). Notably, in the univariate analysis, the factors associated with a worse recurrence-free survival (RFS) were spread-through-air-space (STAS) status (HR =2.131, 95% CI: 1.104-4.112; P=0.02), male sex (HR =1.693, 95% CI: 1.048-2.735; P=0.03), smoking history (HR =1.817, 95% CI: 1.126-2.931; P=0.01), and tumor size >2 cm (HR =1.832, 95% CI: 1.138-2.949; P=0.01). Conclusions:MP component and risk factors might be considered critical features for patients with stage I lung adenocarcinomas and may inform the selection of patients who may benefit from adjuvant chemotherapy although no randomized evidence is available.

The persistent challenge of diabetic wound healing arises from chronic inflammation, which disrupts the immunometabolic microenvironment. This dysregulated microenvironment exhibits remarkable chirality, but how the stereochemical specificity governs host immunometabolism networks remains elusive. In this study, we engineered chiral gold nanoparticles (L/D-AuNPs) to modulate immunometabolic interactions, thereby significantly promoting diabetic wound healing. To align with the chiral characteristics of the vimentin intermediate filaments (VIFs), L/D-AuNPs with mirror-symmetric windmill-like configurations were synthesized using a seed-mediated growth method. In diabetic murine wounds, L-AuNPs demonstrated superior therapeutic efficacy, enhancing wound healing rate by 29 % compared to the control group. Mechanistic studies revealed that L-AuNPs upregulated the expression of the intermediate filaments vimentin, enhancing fibroblast migration. Concomitant mechanotransduction activated the TGF-β/Slug signaling axis, driving nicotinamide metabolic reprogramming in fibroblasts, which subsequently polarized macrophages toward an anti-inflammatory M2 phenotype. This immunometabolic crosstalk was further validated by single-cell transcriptomic profiling of diabetic patient skin specimens. Based on this finding, we combined L-AuNPs with exogenous nicotinamide, which further accelerated wound regeneration through a significant synergistic effect. This study reveals that chiral AuNPs can promote tissue repair by modulating immunometabolic interactions, providing a novel therapeutic strategy for diabetic wound healing.

OBJECTIVES:To investigate the mechanisms by which mesenchymal stem cells (MSCs) contribute to erlotinib resistance in non-small cell lung cancer (NSCLC). METHODS:HCC827 NSCLC cells were treated with MSC-conditioned medium (MSC-CM). Cell viability and apoptosis were evaluated using MTT assays and flow cytometry, respectively. Protein and mRNA expression levels were assessed by western blotting and quantitative real-time PCR. For in vivo validation, a xenograft model was established by co-injecting HCC827 cells and MSCs into NOD/SCID mice. RESULTS:MSC-CM significantly increased cell viability and reduced apoptosis in HCC827 cells following erlotinib treatment, indicating enhanced drug resistance. Mechanistically, MSC-secreted hepatocyte growth factor (HGF) activated AKT and ERK1/2 phosphorylation, thereby bypassing EGFR inhibition by erlotinib. Neutralization of HGF restored erlotinib sensitivity in MSC-CM-treated HCC827 cells. Furthermore, osteopontin (OPN) was transcriptionally upregulated and acted as a resistance enhancer. Inhibition of OPN attenuated MSC-CM-mediated resistance. In vivo, tumors derived from co-injected MSCs and HCC827 cells exhibited significantly greater volume and weight after erlotinib treatment compared to control tumors. CONCLUSIONS:This study identifies a novel MSC-mediated resistance mechanism in which MSC-derived HGF activates compensatory AKT/ERK1/2 signaling, circumventing EGFR blockade by erlotinib. Concurrent upregulation of OPN in NSCLC cells forms a synergistic survival axis under erlotinib pressure. These findings suggest that targeting MSC-derived HGF and tumor-derived OPN may offer promising strategies to overcome erlotinib resistance in NSCLC.

Nipple-sparing mastectomy (NSM) with autologous tissue reconstruction offers excellent cosmetic outcomes but can be complicated by skin necrosis. This study aimed to investigate the risk factors for skin necrosis after NSM with deep inferior epigastric perforator (DIEP) flap reconstruction, focusing on the impact of circumferential periareolar incision length. A retrospective review of 61 patients who underwent NSM followed by DIEP flap reconstruction between 2020 and 2023 was conducted. Data on patient demographics, breast characteristics, incision type, and skin necrosis outcomes were collected. The overall rate of the mastectomy skin flap or nipple-areola complex (NAC) was 42.6

Background Treatment guidelines recommend neoadjuvant or adjuvant chemotherapy, with or without immune checkpoint inhibitors, for resectable non-small-cell lung cancer (NSCLC). We report the interim results for the phase 3 RATIONALE-315 study, which aimed to investigate perioperative tislelizumab for the treatment of resectable NSCLC. Methods RATIONALE-315 is a randomised, double-blind, placebo-controlled phase 3 trial conducted at 50 sites (hospitals or academic research centres) in China. Patients (aged >= 18 years) with untreated stage II-IIIA squamous or non-squamous NSCLC were randomly assigned (1:1) to neoadjuvant tislelizumab 200 mg or placebo intravenously every 3 weeks, plus platinum-based doublet chemotherapy followed by surgery and adjuvant tislelizumab 400 mg or placebo every 6 weeks. Dual primary endpoints were major pathological response rate and event-free survival, analysed by intention to treat. Safety was also assessed in all patients who received at least one dose of study treatment. RATIONALE-315 is registered with ClinicalTrials.gov, NCT04379635, and is active but not recruiting. Findings Between June 8, 2020, and Aug 31, 2022, 453 patients were assigned to tislelizumab (n=226) or placebo (n=227). The median age of patients was 620 years (IQR 560-670). 410 (91%) of 453 patients were male and 43 (9%) were female. As of Aug 21, 2023 (data cutoff for the interim analysis of event-free survival), median duration of follow-up was 220 months (IQR 155-280). Tislelizumab significantly improved event-free survival versus placebo (stratified hazard ratio 056 [95% CI 040-079]; one-sided p=00003). The major pathological response rate was significantly higher in the tislelizumab group (56% [95% CI 50-63]) than in the placebo group (15% [11-20]; difference 41% [33-49]; one-sided p<00001). Grade 3 or worse adverse events and serious treatment-related adverse events occurred in 163 (72%) of 226 patients and 35 (15%) of 226 patients, respectively, in the tislelizumab group, and in 150 (66%) and 18 (8%) patients, respectively, in the placebo group. The most common grade 3 or worse treatment-related adverse event was decreased neutrophil count (138 [61%] of 226 in the tislelizumab group vs 134 [59%] of 226 in the placebo group). 31 (14%) of 226 patients in the tislelizumab group and 45 (20%) of 227 patients in the placebo group died during the study. Interpretation Perioperative tislelizumab plus neoadjuvant chemotherapy showed a clinically meaningful and statistically significant improvement in efficacy and a manageable safety profile compared with neoadjuvant chemotherapy in patients with resectable stage II-IIIA NSCLC.

BACKGROUND:Esophageal cancer is the 11th most common malignancy and the 7th leading cause of cancer-related death globally. Identifying key molecules and underlying mechanisms in the progression of esophageal cancer represents an effective strategy for developing novel therapeutic approaches. METHODS:DDX18 expression in clinical specimens was evaluated by immunohistochemistry and western blot analysis. Functional assays were performed in cells with either DDX18 knockdown or overexpression. Dual luciferase reporter assays and chromatin immunoprecipitation (ChIP) were conducted to validate the interaction between YY1 and the DDX18 promoter. A xenograft tumor model was utilized to investigate the role of DDX18 in vivo in esophageal cancer. RESULTS:DDX18 was found to be markedly overexpressed in esophageal cancer, with its levels significantly higher in patients with pathological grade III compared to those with grades I-II. In vitro, DDX18 enhanced cell proliferation, migration, and invasion, while concurrently suppressing apoptosis. Furthermore, DDX18 promoted epithelial-mesenchymal transition (EMT) and activated the AKT/mTOR signaling pathway. The use of AKT inhibitors effectively abrogated the oncogenic effects of DDX18. Dual luciferase and ChIP assays confirmed that YY1 binds to and stimulates DDX18 transcription. In rescue experiments, YY1 countered the inhibitory effects of DDX18 knockdown on cell proliferation, EMT, and AKT/mTOR activation. In vivo, DDX18 knockdown resulted in reduced tumor growth. CONCLUSIONS:The transcription of DDX18 was activated by YY1, and DDX18 promoted tumor cell growth and EMT through the AKT/mTOR signaling pathway in esophageal cancer cells.

Background:Breast cancer (BC) is the most common cancer among women worldwide, with 2.3 million new cases and 685 000 deaths annually. It has the highest incidence in North America, Europe, and Australia and lower rates in parts of Asia and Africa. Risk factors include age, family history, hormone replacement therapy, obesity, alcohol consumption, and lack of physical activity. BRCA1 and BRCA2 gene mutations significantly increase the risk. The 5-year survival rate is over 90% in developed countries but lower in developing ones. Early screening and diagnosis, using mammography and MRI, are crucial for reducing mortality. In recent years, significant progress has been made in studying BC immunophenotyping, particularly in multicolor flow cytometry, molecular imaging techniques, and tumor microenvironment analysis. These technologies improve diagnosis, classification, and detection of minimal residual disease. Novel immunotherapies targeting the tumor microenvironment, like CAR-T cell therapy, show high efficiency and fewer side effects. High levels of tumor-infiltrating lymphocytes correlate with better prognosis, while immune checkpoint molecules (PD-1, PD-L1) help cancer cells evade the immune system. Tumor-associated macrophages promote invasion and metastasis. Blocking molecules like CTLA-4, LAG-3, and TIM-3 enhance antitumor responses, and cytokines like IL-10 and TGF-beta aid tumor growth and immune evasion. Mendelian randomization (MR) studies use genetic variants to reduce confounding bias and avoid reverse causation, providing robust causal inferences about immune cell phenotypes and BC. This approach supports the development of precision medicine and personalized treatment strategies for BC.Methods:This study aims to conduct MR analysis on 731 immune cell phenotypes with BC in the BCAC and Finngen R10 datasets, followed by a meta-analysis of the primary results using the inverse-variance weighted (IVW) method and multiple corrections for the significance P-values from the meta-analysis. Specifically, the study is divided into three parts: First, data on 731 immune cell phenotypes and BC are obtained and preprocessed from the GWAS Catalog and Open GWAS (BCAC) and the Finngen R10 databases. Second, MR analysis is performed on the 731 immune cell phenotypes with BC data from the BCAC and Finngen R10 databases, followed by a meta-analysis of the primary results using the IVW method, with multiple corrections for the significance P-values from the meta-analysis. Finally, the positively identified immune cell phenotypes are used as outcome variables, and BC as the exposure variable for reverse MR validation.Results:The study found that two immune phenotypes exhibited strong significant associations in MR analysis combined with meta-analysis and multiple corrections. For the immune phenotype CD3 on CD28+ CD4-CD8- T cells, the results were as follows: in the BCAC dataset, the IVW result was odds ratio (OR) = 0.942 (95% CI: 0.915-0.970, P=6.76x10-5), beta=-0.059; MR Egger result was beta=-0.095; and the weighted median result was beta=-0.060. In the Finngen R10 dataset, the IVW result was OR=0.956 (95% CI: 0.907-1.01, P=0.092), beta=-0.045; MR Egger result was beta=-0.070; and weighted median result was beta=-0.035. The beta values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR=0.945 (95% CI: 0.922-0.970, P=1.70x10-5). After Bonferroni correction, the significant P-value was P=0. 01, confirming the immune phenotype as a protective factor against BC. For the immune phenotype HLA DR on CD33- HLA DR+, the results were as follows: in the BCAC dataset, the IVW result was OR=0.977 (95% CI: 0.964-0.990, P=7.64x10-4), beta=-0.023; MR Egger result was beta=-0.016; and the weighted median result was beta=-0.019. In the Finngen R10 dataset, the IVW result was OR=0.960 (95% CI: 0.938-0.983, P=6.51x10-4), beta=-0.041; MR Egger result was beta=-0.064; and weighted median result was beta=-0.058. The beta values were consistent in direction across all three MR methods in both datasets. The meta-analysis of the IVW results from both datasets showed OR=0.973 (95% CI: 0.961-0.984, P=3.80x10-6). After Bonferroni correction, the significant P-value was P=0.003, confirming this immune phenotype as a protective factor against BC. When the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ were used as outcomes and BC was used as exposure, the data processing and analysis procedures were the same. The MR analysis results are as follows: data from the FinnGen database regarding the effect of positive immune phenotypes on malignant neoplasm of the breast indicated a beta coefficient of -0.011, OR = 0.99 (95% CI: -0.117-0.096, P=0.846); data from the BCAC database regarding favorable immune phenotypes for BC demonstrated a beta coefficient of -0.052, OR=0.095 (95% CI: -0.144-0.040, P=0.266). The results suggest insufficient evidence in both databases to indicate that BC inversely affects these two immune cell phenotypes.Conclusions:Evidence suggests that the immune cell phenotypes CD3 on CD28+ CD4-CD8- T cells and HLA DR on CD33- HLA DR+ protect against BC. This protective effect may be achieved through various mechanisms, including enhancing immune surveillance to recognize and eliminate tumor cells; secreting cytokines to inhibit tumor cell proliferation and growth directly; triggering apoptotic pathways in tumor cells to reduce their number; modulating the tumor microenvironment to make it unfavorable for tumor growth and spread; activating other immune cells to boost the overall immune response; and inhibiting angiogenesis to reduce the tumor's nutrient supply. These mechanisms work together to help protect BC patients and slow disease progression. Both immune cell phenotypes are protective factors for BC patients and can be targeted to enhance their function and related pathways for BC treatment.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the electrophoretic blots shown in Fig. 3A‑a, the data shown for the BMP7 and GAPDH bands were strikingly similar, such that it appeared that the same data had been included in this figure part to show the results from the differently performed experiments. The authors were able to re‑examine their original data, and realized that the BMP7 bands had inadvertently been included in this figure twice. The revised version of Fig. 3, now incorporating the correct data for the GAPDH bands in Fig. 3A‑a, is shown on the next page. The authors can confirm that the error made in asembling this figure did not have a significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 29: 1016‑1024 2012; DOI: 10.3892/ijmm.2012.948].

9548 Background: TIL therapy, as one of the most promising adaptive cellular immunotherapy, has shown success in metastatic melanoma, with a median overall response rate (ORR) of 28% and median PFS (progression free survival) of 7.2 months. This phase I clinical trial aimed to explore the safety, feasibility, and efficacy of TILs monotherapy in Asian metastatic melanoma pts. Methods: Pts with metastatic melanoma who had progressed on standard therapies, had both resectable and measurable tumors were eligible to be enrolled. Pts received a lymphodepletion regimen which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m 2 ) for 5 days, approximately 24 hours before receiving the intravenous autologous LM103 (TILs) infusion and then high dose IL-2 for 6 doses (200000IU/Kg, 1 dose per day. Doses can be adjusted based on pts tolerance to support T cell survival and proliferation. Results: Twelve pts (aged 26-68 yrs) with metastatic melanoma were enrolled and treated, including 8 males. Among the primary melanoma types, 6 were acral, 3 mucosal, 2 unknown, and 1 cutaneous. 7 pts had distant organ metastases. As of Jan 2025, 8 out of 12 pts were assessable, one could not be evaluated due to rapid brain metastases and 3 remained under safety observation (median follow-up, 6 wks; range, 2-48 wks). Resected tumors used for TIL production were from 8 metastatic lymph nodes and 4 subcutaneous nodules. The infused autologous TIL contained 8.24-19.47X10 10 viable cells. The median duration of IL-2 infusion were 5.08 days, with a median dose of 13.75 IU/Kg/day. The most frequent treatment-emergent adverse events (TEAEs) were myelosuppression (100%), fever (100%), anemia (100%), and hypotension (100%). Grade 3-4 TEAEs included neutropenia (100%), lymphopenia (100%), leukopenia (100%), fever (75%), thrombocytopenia (62.5%), and anemia. The ORR was 50% (4/8, 4PR, 2SD, 2PD) per RECIST v1.1. The median PFS was not reached and the longest PFS was 11.4 months. Responders demonstrated a larger number of T cell clones, higher T cell receptor (TCR) diversity (Inverse Simpson Index), and lower TCR clonality compared to non-responders ( P =0.031, P=0.049 and P=0.033 ), based on real time peripheral monocytes analysis. These findings suggest that the LM103 in responders recognized a broader antigen spectrum . Notably, about 50% of initial TCR clones can be detected 18 wks post-infusion, suggesting LM103 persistence. Post-hoc analysis revealed that responders had a CD8+ T-cells proportion of 60-80%, while non-responders exhibited extreme proportions (<10% or >80%). Conclusions: LM103 was well tolerated and demonstrated durable responses in Asian patients with advanced melanoma. Patients with 60-80% CD8+T-cell proportions are more likely to respond to TIL therapy. Clinical trial information: CTR20233999 .