Natural killer (NK) cells are key for tumor immune defense. Tissue-resident NK subsets often differ from classical CD16+ NKs and can be immunosuppressive. The exact traits and mechanisms of these tissue-resident NKs in the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) are still unclear. This study aimed to comprehensively analyze NK cells in the NSCLC tumor microenvironment to identify distinct tissue-resident subsets, assess their clinical relevance, and investigate their functional properties and underlying mechanisms in shaping immunosuppression. We identified CD49a+ NK cells as a distinct tissue-resident subset in non-small cell lung cancer surgical specimens. Single-cell RNA sequencing revealed that this subset is associated with poor pathological response to neoadjuvant therapy. The abundance of CD49a+ NK cells negatively correlates with the formation of tertiary lymphoid structures (TLS). These cells exhibit an altered phenotype, characterized by upregulated immune checkpoint genes, downregulated cytotoxicity-related genes, and uniquely elevated expression of CSF-1. This CD49a+ NK cell subset is functionally linked to driving M2 macrophage polarization, and M2 polarization tends to inversely correlate with TLS density. Our findings indicate that CD49a+ NK cells contribute to the induction of M2 macrophage differentiation within the tumor stroma and are unfavorable for TLS formation. Our findings identify a specific CD49a+ tissue-resident NK cell subset that fosters an immunosuppressive microenvironment in NSCLC by impairing TLS formation and driving M2 macrophage polarization, a mechanism that likely contributes to adverse responses to neoadjuvant therapy.

e20073 Background: Immunotherapy combined with chemotherapy as neoadjuvant treatment for NSCLC has demonstrated significant clinical benefits, yet various treatment regimens continue to be explored during neoadjuvant therapy for resectable NSCLC. We report here the efficacy and safety of adebrelimab combined with anlotinib and chemotherapy in neoadjuvant treatment for stage II-III NSCLC. Methods: Eligible patients (pts) were resectable stage II and III (IIIA and T3N2M0 IIIB) NSCLCs without EGFR/ALK/ROS1 alterations. Patients received neoadjuvant treatment with adebrelimab＋anlotinib , 4 cycles and chemotherapy 3-4 cycles, followed by surgical resection.The primary endpoint was major pathological response (MPR), secondary endpoints inluding pathological complete response rate (pCR), objective response rate (ORR), event free survival (EFS), overall survival (OS), and safety (NCI-CTCAE v5.0). Results: From March 2025 to January 2026, 44 pts was screened and 37 eligible pts enrolled. 81.1% were male, 62.2% had squamous cell carcinoma, 78.4% of pts had a history of smoking, and 75.7% were stage III pts. As of January 24, 2026, all 37 pts received at least one cycle of neoadjuvant therapy, with 28 pts completed the full four-cycle regimen. Surgery was performed in 25 pts (1 pts refused surgery, 1 pts withdrew informed consent, and1 pts died unexpectedly), 100% achieved R0 resection. Pathological assessment was completed in 25 patients, demonstrating pCR in 14 (56.0%) and MPR in 18 (72.0%). 34 pts had an objective response per RECIST v1.1, including 6 with complete response and 17 with partial response. The ORR was 67.6% and DCR was 97.1%. 35 pts were included in the safety analysis. Grade ≥3 treatment-related adverse events included thrombocytopenia (11.4%), lymphopenia (8.6%) and leukopenia (5.7%). One patient died due to an accidental fall. No surgical delays occurred due to adverse events. No deaths related to tumor treatment were identified. Conclusions: Adebrelimab in combination with anlotinib and chemotherapy as neoadjuvant therapy showed a high proportion of MPR and pCR for resectable stage II-III NSCLC, and the safety profile was well tolerated. Future clinical studies with larger sample sizes are needed to be validated. Clinical trial information: ChiCTR2500100571.

ABSTRACT Cellular senescence, a state of irreversible cell cycle arrest accompanied by a senescence‐associated secretory phenotype (SASP), plays dual roles in cancer biology. Initially recognized as a tumor‐suppressive mechanism by halting the proliferation of damaged cells, senescence paradoxically fosters tumor progression through SASP‐mediated immunosuppression and chronic inflammation. Thus, the role of senescent cells in tumors still needs to be further elucidated. Our review comprehensively examines the triggers and molecular pathways of senescence. We also summarized the characteristics and functions of senescent tumor and nontumor cells, delineating the heterogeneous tumor senescence microenvironment. Here, we highlight the functional reprogramming of senescent cells, including enhanced stemness, secretome and metabolome reprogramming, which can sustain tumorigenesis and therapeutic resistance. Furthermore, we discuss emerging therapeutic strategies, notably the “one‐two punch” approach to overcome therapy resistance. By integrating recent advances in senescence‐targeted therapies, our review underscores the necessity of context‐specific strategies to harness senescence's tumor‐suppressive effects while mitigating its protumorigenic consequences. These insights provide a roadmap for developing precision therapies and refining biomarker‐driven approaches to improve cancer treatment outcomes.

Immunotherapy has revolutionized cancer treatment, offering significant efficacy across various cancer types. However, hyperprogressive disease (HPD)—a severe and unexpected acceleration of tumor growth—poses a critical challenge, as some patients experience this adverse effect. Early and accurate identification of HPD risk is essential for optimizing immunotherapy strategies and improving patient outcomes. To address this, we developed a machine learning-based predictive model for HPD risk across cancer types, integrating clinical and molecular data. This study analyzed data from 1, 005 patients with solid tumors treated with at least one dose of immune checkpoint inhibitors between 2018 and 2024. After stringent data preprocessing, feature selection was performed using chi-square and Fisher’s exact tests to identify significant variables associated with HPD. Logistic regression evaluated feature importance, accounting for multicollinearity, correlation, and interpretability. A random forest algorithm was then employed to construct a predictive model based on selected features. From an initial pool of 44 variables, eight features were identified as significant predictors of HPD, including HPD-associated genes, immunotherapy resistance genes, cancer type, bone metastasis, the number of metastatic sites, lactate dehydrogenase levels, neutrophil-to-lymphocyte ratio, and treatment regimen. Patients lacking pre-immunotherapy genetic and blood test data for the selected features were excluded, resulting in a final cohort of 363 patients across 17 cancer types, including 52 HPD cases and 311 non-HPD cases. The model demonstrated strong predictive performance, achieving a cross-validated AUC of 0.87, sensitivity of 0.90, and specificity of 0.78. On an independent test set, the model attained an AUC of 0.71, sensitivity of 0.70, specificity of 0.73, and overall accuracy of 73%. Using the same eight features, a traditional logistic regression model was constructed (AUC = 0.66) and found to be less effective than the machine learning model. We identified eight statistically and clinically significant predictors of HPD and developed the first high-sensitivity pan-cancer predictive tool combining molecular and clinical features. This machine learning-based approach enhances HPD risk stratification, assisting clinicians in tailoring immunotherapy and mitigating risks, ultimately improving patient outcomes across cancer types. Haitao Wang, Lili Wang, Yu Zhang, Hongzheng Li, Nan Li, Qijie Jian, Yaxian Wang, Zhijian Song, Fei Pang, Kai Wang. A machine learning model for predicting hyperprogressive disease risk in cancer immunotherapy: Integrating clinical and molecular data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4626.

AbstractBackgroundEpidermal growth factor receptor (EGFR) mutations are key drivers in a significant portion of non‐small‐cell lung cancer (NSCLC) patients. While third‐generation EGFR‐tyrosine kinase inhibitors (TKIs) such as osimertinib have demonstrated efficacy, the management of patients who continue to experience disease progression during treatment remains challenging. The emergence of drug resistance, including the development of secondary mutations, necessitates exploration of alternative treatment strategies. This study aims to evaluate and observe the efficacy and safety of almonertinib combined with anlotinib in patients after cancer progression during third‐generation EGFR‐TKI therapy.MethodsIn this retrospective analysis, we included EGFR‐mutated NSCLC patients who were resistant to third‐generation EGFR‐TKIs. All patients were treated with almonertinib combined with anlotinib. The clinical characteristics, treatment history, clinical benefits, and adverse events of these patients were retrospectively collected.ResultsA total of 16 eligible patients were included in the analysis. The results revealed that combination therapy with almonertinib and anlotinib was effective in this patient cohort. The overall response rate was 25% and the disease control rate was 93.75%. The 6 and 12 months of PFS rates were 92.9% (95% confidence interval [CI] 80.3%, 100.0%) and 84.4% (95% CI 66.6%, 100.0%), respectively. Moreover, this combination therapy was generally well‐tolerated, with manageable adverse events.ConclusionOur retrospective analysis suggests that almonertinib and anlotinib combination therapy may represent a viable option for EGFR‐mutated NSCLC patients who have progressed on third‐generation EGFR‐TKIs, especially for those with posterior lines and no standard treatment options. Further investigation and larger clinical trials are warranted to validate these observations and refine treatment guidelines.

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

BACKGROUND The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis. AIM To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN. METHODS From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility. RESULTS After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97. CONCLUSION This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.

AIMS:PD-1 block was reported to impair opioid-induced antinociception and affect cognitive function in rodents and non-human primates. This prospective multicenter cohort study aims to investigate the possible impact of neoadjuvant immunotherapy with PD-1 antibody on perioperative analgesic effect of opioids and postoperative delirium (POD) for non-small-cell lung cancer (NSCLC) patients. METHODS:Eighty-four NSCLC patients from three medical centers with neoadjuvant chemoimmunotherapy (nCIT) or chemotherapy (nCT) were enrolled. The primary outcome is the total perioperative opioid consumption defined as the sum of intraoperative and postoperative opioid use within 3 days after surgery. Secondary outcomes compromise of incidence of POD, pain intensity, and number of analgesic pump press. Tumor prognostic parameters and perioperative change of inflammatory cytokines and soluble PD-L1 level were also recorded. RESULTS:Eighty-one patients were included in the final analysis. The total opioid consumption (sufentanil equivalent) perioperatively in the nCIT group was significantly higher than that in the nCT group, with mean difference of 60.39 μg, 95% CI (25.58-95.19), p < 0.001. Multiple linear regression analysis showed that nCIT was correlated with increased total opioid consumption (β = 0.305; 95% CI, 0.152-0.459; p < 0.001). The incidence of moderate-to-severe pain and cumulative analgesic pump press within 72 h was significantly higher in subjects with nCIT. There is no statistical difference in incidence of POD between groups within 72 h after surgery. The pathologic complete response rate and perioperative serum IL-6 level were higher in the nCIT group than in the nCT group. CONCLUSION:Patients with NSCLC receiving nCIT warrant increased opioid consumption perioperatively and suffered from more postoperative pain. CLINICAL TRIAL REGISTRATION:NCT05273827.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant gastrointestinal tumor with a poor prognosis. Serum biomarker carbohydrate antigen 19-9 (CA19-9) was the only well-established biomarker for PDAC with inadequate efficacy. This present study aimed to determine the ability of PIVKA-II to discriminate PDAC from pancreatic benign lesions and predict vascular invasion preoperatively. Methods: Patients who underwent pancreatic surgery from 2017 to 2020 were enrolled. We examined the differential diagnostic ability of protein induced by vitamin K absence II (PIVKA-II), CA19-9, and their combination and 138 with PDAC evaluated the predictive value of PIVKA-II for vascular invasion in PDAC. Methods: A total of 138 patients with PDAC and 90 patients with pancreatic benign lesions who underwent pancreatic surgery from 2017 to 2020 were enrolled. The clinicopathological characteristics were recorded. Results: There was a significant difference in levels of serum PIVKA-II between PDAC patients and patients with pancreatic benign lesions (p < 0.001). When the cut-off value was set to 28.9 mAU/mL according to the ROCs, the AUC, sensitivity, and specificity of PIVKA-II were 0.787, 68.1%, and 83.3%, respectively. The combined PIVKA-II and carbohydrate antigen 19-9 (CA19-9) enhanced the diagnostic accuracy, and the AUC, sensitivity, and specificity were 0.945, 87.7%, and 94.4%, respectively. PIVKA-II > 36.4 mAU/mL were independent predictive factors of vascular invasion in PDAC (p < 0.001). Conclusion: PIVKA-II was a potential diagnostic biomarker to differentiate PDAC from pancreatic benign lesions. PIVKA-II was complementary to CA19-9, and the combination enhanced the differential diagnostic performance. PIVKA-II > 36.4 mAU/mL was an independent predictive factor of vascular invasion in PDAC.

The annexin superfamily (ANXA) is made up of 12 calcium (Ca 2+ ) and phospholipid binding protein members that have a high structural homology and play a key function in cancer cells. However, little research has been done on the annexin family’s function in pan-cancer. We examined the ANXA family’s expression in various tumors through public databases using bioinformatics analysis, assessed the differences in ANXA expression between tumor and normal tissues in pan-cancer, and then investigated the relationship between ANXA expression and patient survival, prognosis, and clinicopathologic traits. Additionally, we investigated the relationships among TCGA cancers’ mutations, tumor mutation burden (TMB), microsatellite instability (MSI), immunological subtypes, immune infiltration, tumor microenvironment, immune checkpoint genes, chemotherapeutics sensitivity, and ANXAs expression. cBioPortal was also used to uncover pan-cancer genomic anomalies in the ANXA family, study relationships between pan-cancer ANXA mRNA expression and copy number or somatic mutations, and assess the prognostic values of these variations. Moreover, we investigated the relationship between ANXAs expression and effectiveness of immunotherapy in multiple cohorts, including one melanoma (GSE78220), one renal cell carcinoma (GSE67501), and three bladder cancer cohorts (GSE111636, IMvigor210 and our own sequencing dataset (TRUCE-01)), and further analyzed the changes of ANXAs expression before and after treatment (tislelizumab combined with nab-paclitaxel) of bladder cancer. Then, we explored the biological function and potential signaling pathway of ANXAs using gene set enrichment analysis (GSEA), and first conducted immune infiltration analysis with ANXAs family genes expression, copy number, or somatic mutations of bladder cancer by TIMER 2.0. Most cancer types and surrounding normal tissues expressed ANXA differently. ANXA expression was linked to patient survival, prognosis, clinicopathologic features, mutations, TMB, MSI, immunological subtypes, tumor microenvironment, immune cell infiltration, and immune checkpoint gene expression in 33 TCGA cancers, with ANXA family members varied. The anticancer drug sensitivity analysis showed that ANXAs family members were significantly related to a variety of drug sensitivities. In addition, we also discovered that the expression level of ANXA1/2/3/4/5/7/9/10 was positively or negatively correlated with objective responses to anti-PD-1/PD-L1 across multiple immunotherapy cohorts. The immune infiltration analysis of bladder cancer further showed the significant relationships between ANXAs copy number variations or mutation status, and infiltration level of different immune cells. Overall, our analyses confirm the importance of ANXAs expression or genomic alterations in prognosis and immunological features of various cancer and identified ANXA-associated genes that may serve as potential therapeutic targets.

ObjectivesDespite the increasing use of computed tomography (CT), chest X-ray (CXR) remains the first-line investigation for suspected lung cancer (LC) in primary care. However, the associations of CXR trajectories, smoking and LC risk remain unknown.MethodsA total of 52,486 participants from the PLCO and 22,194 participants from the NLST were included. The associations of CXR trajectories with LC risk were evaluated with multivariable COX regression models and pooled with meta-analyses. Further analyses were conducted to explore the stratified associations by smoking status and the factors associated with progression and regression in CXR.ResultsCompared to stable negative CXR (CXRSN), HRs (95%CIs) of LC incidence were 2.88(1.50–5.52), 3.86(2.03–7.35), and 1.08(0.80–1.46) for gain of positive CXR (CXRGP), stable positive CXR (CXRSP), and loss of positive CXR (CXRLP), while the risk of LC mortality were 1.58(1.33–1.87), 2.56(1.53–4.29), and 1.05(0.89–1.25). Similar trends were observed across different smoking status. However, LC risk with CXRGP overweighed that with CXRSP among ever smokers [2.95(2.25–3.88) vs. 2.59(1.33–5.02)] and current smokers [2.33(1.70–3.18) vs. 2.26(1.06–4.83)]. Moreover, compared to CXRSN among never smokers, even no progression in CXR, the HRs(95%CIs) of LC incidence were 7.39(5.60–9.75) and 31.45(23.58–41.95) for ever and current smokers, while risks of LC mortality were 6.30(5.07–7.81) and 27.17(21.65–34.11). If participants gained positive CXR, LC incidence risk significantly climbed to 22.04(15.37–31.60) and 71.97(48.82–106.09) for ever and current smokers, while LC mortality risk climbed to 11.90(8.58–16.50) and 38.92(27.04–56.02). CXRLP was associated with decreased LC risk. However, even smokers lost their positive CXR, and the increased risks of LC incidence and mortality did not decrease to non-significant level. Additionally, smoking was significantly associated with increased risk of CXRGP but not CXRLP.ConclusionLC risk differed across CXR trajectories and would be modified by smoking status. Comprehensive intervention incorporating CXR trajectories and smoking status should be recommended to reduce LC risk.

Severe aplastic anemia (SAA) is an immune-mediated bone marrow failure characterized by pancytopenia. This study was aimed at uncovering proteins of plasma that were differentially expressed in SAA patients. 8 SAA patients and 8 health controls were enrolled and detected by data independent acquisition (DIA) technology. 154 differential expression proteins (DEPs) in plasma of SAA patients were identified. GO and KEGG analyses indicated DEPs were mainly involved in the immune system process. Specifically, C-C motif chemokine 18 (CCL18), matrix metalloproteinase-3 (MMP3), histidine-rich glycoprotein (HRG), and lactotransferrin (lactoferrin (Lf)) may play an important role in the immune pathogenesis of SAA. CCL18, MMP3, HRG, and Lf might be potential biomarkers for SAA.

Savolitinib is a tyrosine kinase inhibitor being developed for the treatment of metastatic non–small cell lung cancer (NSCLC) with mesenchymal–epithelial transition (MET) factor exon 14 skipping alterations. However, the role of savolitinib in neoadjuvant therapy for lung cancer remains unclear. Here, we present a case of a 65-year-old woman diagnosed with stage IIIA (cT2bN2M0, eighth TNM stage) upper right lung adenocarcinoma harboring MET exon 14 skipping alterations. After 4 weeks of therapy, a partial response was achieved with neoadjuvant savolitinib, and significant shrinkage in tumor and lymph nodes was observed. We also measured the immune microenvironment of the primary tumor pre- and posttreatment with savolitinib.

Severe aplastic anemia (SAA) is a syndrome of severe bone marrow failure due to hyperfunction of CD8+ T cells. While, the genetic background of SAA is still unknown. In this study, we tried to explore the possible genetic variants in CD8+ T cells of SAA patients.

目的 探讨Toll样受体(TLR)3活化对人脐静脉内皮细胞(HUVECs)凋亡的影响及其机制.方法 将对数生长期的HUVECs随机分为A组、B组、C组、D组、E组和F组,分别以含0.000、0.001、0.010、0.100、1.000、10.000 mg·L-1聚肌胞苷酸[Poly(I:C)]的培养基培养24 h,备用.采用Western blot法检测6组HUVECs中TLR3及pro-caspase-3、caspase-3 P17蛋白相对表达量,并计算caspase-3 P17与pro-caspase-3蛋白相对表达量比值(caspase-3 P17/pro-caspase-3).采用反转录-聚合酶链式反应法检测6组HUVECs中肿瘤坏死因子相关凋亡诱导配体(TRAIL)、死亡受体(DR)4和DR5 mRNA相对表达量.结果 B组、C组、D组、E组、F组细胞中TLR3蛋白相对表达量显著高于A组,C组、D组、E组、F组细胞中TLR3蛋白相对表达量显著高于B组,D组细胞中TLR3蛋白相对表达量显著高于C组,E组、F组细胞中TLR3蛋白相对表达量显著低于D组,F组细胞中TLR3蛋白相对表达量显著低于E组(P<0.05).B组、C组细胞中caspase-3 P17/pro-caspase-3显著低于A组,D组、E组、F组细胞中caspase-3 P17/pro-caspase-3显著高于A组、B组、C组,F组细胞中caspase-3 P17/pro-caspase-3显著低于D组、E组(P<0.05).B组、C组、D组、E组、F组细胞中TRAIL mRNA相对表达量显著高于A组,C组、D组、E组、F组细胞中TRAIL mRNA相对表达量显著高于B组,E组、F组细胞中TRAIL mRNA相对表达量显著高于C组和D组,F组细胞中TRAIL mRNA相对表达量显著低于E组(P<0.05).C组、D组、E组、F组细胞中DR4 mRNA相对表达量显著高于A组和B组,D组、E组、F组细胞中DR4 mRNA相对表达量显著高于C组,E组、F组细胞中DR4 mRNA相对表达量显著高于D组,F组细胞中DR4 mRNA相对表达量显著高于E组(P<0.05).B组、C组、D组、E组、F组细胞中DR5 mRNA相对表达量显著高于A组,E组、F组细胞中DR5相对表达量显著高于B组、C组、D组(P<0.05).结论 Poly(I:C)活化TLR3可能引起HUVECs凋亡,其机制可能涉及外源性凋亡途径TRAIL-DR4/DR5.

Vanderbylia robiniophila (Murrill) B.K. (Huaier) is a kind of higher fungal fruiting body that is parasitic on the trunk of Sophora japonica and Robinia pseudoacacia L.. As a traditional Chinese medicine with a history of more than 1,600 years, Huaier has attracted wide attention for its excellent anticancer activity. A systematic study on the metabolome differences between natural Huaier and artificial cultured Huaier was conducted using liquid chromatography-mass spectrometry in this study. Principal component analysis and orthogonal projection on latent structure-discriminant analysis results showed that cultured Huaier evidently separated and individually separated from natural Huaier, indicating metabolome differences between natural and cultured Huaier. Hierarchical clustering analysis was further performed to cluster the differential metabolites and samples based on their metabolic similarity. The higher contents of amino acids, alkaloids and terpenoids in natural Huaier make it an excellent choice as a traditional Chinese medicine for anticancer or nutritional supplementation. The results of the Bel-7,402 and A549 cell cytotoxicity tests showed that the anticancer activity of natural Huaier was better than that of cultured Huaier. This may be due to the difference in chemical composition, which makes the anticancer activities of natural and cultured Huaier different.

BACKGROUND Whether nab-paclitaxel plus carboplatin as neoadjuvant therapy can benefit patients with resectable squamous cell carcinoma of the lung remains unclear. This prospective study aimed to investigate outcomes in patients with stage IIIA-N2 squamous cell carcinoma of the lung treated with nab-paclitaxel plus carboplatin as neoadjuvant therapy. MATERIAL AND METHODS Patients with stage IIIA-N2 squamous cell carcinoma of the lung were treated with nab-paclitaxel (100 mg/m², days 1, 8, and 15) and carboplatin (5 mg/(mL·min), day 1) for two 21-day cycles. The patients were followed every 3 months for 2 years and every 6 months after that. The primary endpoint was the downstaging rate. Secondary endpoints included objective response rate (ORR), margin-free (R0) resection, pathologic complete response (pCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Among the 36 enrolled patients, 33 completed neoadjuvant chemotherapy, and 23 underwent surgery. The preoperative ORR was 50.0% (18/36). R0 resection was achieved in 22 (95.7%) of 23 patients. Major pathologic response and pCR were achieved in 8 (34.8%) and 2 (8.7%) patients, respectively. The overall downstaging rate was 47.8% (11/23). The median follow-up was 39.8 (32.5-41.0) months. For patients who underwent surgery, the median PFS and OS were 31.4 (95%CI: 10.4-not reached (NR)) and 45.0 (95%CI: 22.6-NR) months, respectively. The most common adverse events were neutropenia, anemia, and leukopenia. CONCLUSIONS This study preliminarily indicated a favorable effect of nab-paclitaxel plus carboplatin as neoadjuvant therapy without significant adverse events for stage IIIA-N2 squamous cell carcinoma of the lung. Future randomized controlled trials are needed to verify these results.

Abstract Blockade of the binding between neonatal Fc receptor and IgG‐Fc reduces circulating IgG, and thus emerges as a potential therapy for IgG‐mediated autoimmune conditions. This was a double blind, randomized, single ascending dose study to evaluate the safety, pharmacokinetics, and pharmacodynamics of HBM9161 (a fully humanized Fc receptor monoclonal antibody) in healthy Chinese volunteers. Subjects were randomized to receive a single s.c. dose of HBM9161 or placebo in a 3:1 ratio in 3 dosing cohorts (340 mg, 510 mg, or 680 mg, respectively), and then followed up for 85 days. Study end points included incidence of adverse event (AE), serum drug concentration, IgG and its subclasses, and anti‐drug antibodies (ADAs). Twenty‐four subjects were randomized. Dose‐dependent reduction of total IgG occurred rapidly from baseline to reach nadir at day 11, then recovered steadily from day 11 to day 85. The mean maximum percentage reductions from baseline total IgG were 21.0 ± 9.3%, 39.8 ± 5.13%, and 41.2 ± 10.4% for subjects receiving HBM9161 340 mg, 510 mg, and 680 mg, respectively. The exposure of HBM9161 (areas under the curve [AUCs] and peak plasma concentration [Cmax]) increased in a more than dose‐proportional manner at the dose examined. All reported AEs were mild in severity. The most reported AEs in the HBM9161 groups were influenza‐like illness and rash. Two subjects developed ADA during the study period. A single s.c. dose of HBM9161 results in sustained and dose‐dependent IgG reduction, and was well‐tolerated at a dose up to 680 mg in Chinese subjects. The data warrant further investigation of its effects in IgG‐mediated autoimmune disorders.

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement characterizes a subgroup of patients who show sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients. Methods: We retrospectively analyzed 96 patients with NSCLC with ALK detected by immunohistochemical staining (VENTANA anti-ALK(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of ALK fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed. Results: Among the 96 patients with immunohistochemically identified ALK fusions, 80 (83%) were confirmed by next-generation sequencing. TP53 mutation was the most commonly co-occurring mutation with ALK rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog (KRAS) G12, 1 epidermal growth factor receptor (EGFR) 19del, and 1 MET exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions were identified in 95% of ALK-rearranged patients, with 16.2% of them also harboring additional non-EML4- ALK fusions. Nineteen non-EML4 translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring PIK3R2 alterations showed a trend toward shorter progression-free survival (6 vs. 13 months, P=0.064) and significantly shorter overall survival (11 vs. 32 months, P=0.004) than did PIK3R2-wild-type patients. Patients with concomitant alterations in PI3K the signaling pathway also had a shorter median overall survival than those without such alterations (23 vs. 32 months, P=0.014), whereas progression-free survival did not differ significantly. Conclusions: The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy.