The clinical benefit of extending tumor treating fields (TTFields) beyond concurrent chemoradiotherapy (CRT) for newly diagnosed glioblastoma (ndGBM) is unclear. This multi-institutional retrospective study compared patients who continued TTFields into adjuvant temozolomide (CRT-TT, n = 68) versus those who discontinued after CRT (CRT-T, n = 32). With a median follow-up of 36.9 months, median progression-free survival (mPFS) did not significantly differ between the groups (12.8 vs. 12.5 months; hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.57-1.59; p = 0.853) nor did median overall survival (mOS) (20.6 vs. 16.6 months; HR 0.73, 95% CI 0.43-1.27; p = 0.267). Additionally, continuing TTFields into the adjuvant phase did not increase scalp toxicity. Although a numerically longer OS was seen in the CRT-TT group, the lack of statistical significance may reflect limited power and non-randomized allocation. These findings underscore the need for further investigation.

Purpose:The combination of radiotherapy with immunotherapy holds synergistic potential, yet its role in the neoadjuvant treatment of breast cancer remains underexplored. This single-center, retrospective pilot study aimed to explore the preliminary efficacy and safety of integrating stereotactic body radiotherapy (SBRT) with chemoimmunotherapy as a novel neoadjuvant regimen for a small cohort of patients with high-risk, locally advanced breast cancer. Patients and Methods:Between June 2023 and August 2025, 20 patients received neoadjuvant SBRT (18Gy/3 fractions for node-positive; 24Gy/3 fractions for node-negative disease) concurrently with chemoimmunotherapy (various anti-PD-1/bispecific antibodies plus chemotherapy), followed by surgery. Key endpoints were pathological complete response (pCR, ypT0/Tis ypN0), near-pCR (Residual Cancer Burden [RCB] class 0 or I), objective response rate (ORR), and safety. Results:The cohort included triple-negative breast cancer (TNBC, 35%) and hormone receptor-positive/HER2-negative breast cancer of the Luminal B subtype (Luminal B/HER2-, 50%). Most had cT2 (75%) and node-positive (75%) disease. The median number of chemoimmunotherapy cycles were 8, with 80% receiving an AC-T backbone. The overall pCR rate was 45% (9/20). Efficacy varied by subtype: the pCR rate was 85.7% (6/7) in TNBC and 20% (2/10) in Luminal B/HER2- disease. Notably, 100% of TNBC and 40% of Luminal B/HER2- patients achieved near-pCR (RCB 0/I). ORR was 90%. Grade 3-4 adverse events occurred in 25% of patients, with no treatment-related mortality. Conclusion:In this single-center, retrospective pilot study, early integration of SBRT with chemoimmunotherapy demonstrated promising antitumor activity, particularly high pCR rates in TNBC and induction of deep pathological responses (RCB 0/I) in Luminal B/HER2- disease, with a manageable safety profile. Observed in a heterogeneous cohort, these preliminary findings highlight potential efficacy but require cautious interpretation and warrant validation in larger, prospective trials.

BACKGROUND:Craniofacial postherpetic neuralgia (PHN), though relatively uncommon, presents significant clinical challenges through chronic headache and facial pain manifestations. This study aimed to assess the efficacy of ultrasound-guided peripheral nerve radiofrequency ablation (RFA) for craniofacial zoster-related pain. METHODS:A total of 91 patients with cephalofacial PHN admitted to the Renmin Hospital of Wuhan University from January 2023 and December 2024 were retrospectively analyzed. All patients were treated with ultrasound-guided peripheral nerve (supraorbital, infraorbital, mental, and greater occipital nerves) RFA. Pain intensity, sleep quality, and quality of life were objectively quantified using standardized metrics: Visual Analog Scale (VAS) for nociceptive assessment, 5-item validated questionnaire for sleep evaluation, and 36-Item Short Form Health Survey (SF-36) for multidimensional functional analysis. Both pharmacological protocols and post-RFA complications were systematically documented. RESULTS:RFA demonstrated significant therapeutic outcomes: VAS scores decreased from 6.7 ± 1.0 to 2.2 ± 1.3 (p < 0.001), accompanied by SF-36 improvement and enhanced sleep quality (6.0 ± 3.4 vs. 10.7 ± 2.4; p < 0.001). Medication requirements substantially reduced, with pregabalin decreasing from 292 ± 74 mg to 70 ± 91 mg and tramadol from 163 ± 61 mg to 38 ± 63 mg (both p < 0.001). Postoperative complications analysis (n = 64) revealed cutaneous hypoesthesia as the most prevalent (82.8 %, 53/64), followed by puncture-site edema (57.8 %, 37/64). Less frequent occurrences included periorbital ecchymosis (15.6 %, 10/64), de novo neuralgia (7.8 %, 5/64), transient visual disturbances (4.7 %, 3/64), and localized infections (3.1 %, 2/64). CONCLUSION:Ultrasound-guided peripheral nerve RFA effectively alleviates craniofacial zoster-related pain with concomitant improvements in quality of life and sleep metrics, though sustained vigilance regarding long-term sequelae remains clinically imperative.

Introduction Immunotherapy combined with chemotherapy has shown potential in improving the pathological complete response (pCR) rate in luminal-type breast cancer. This study explores whether the addition of stereotactic body radiotherapy (SBRT) and the bispecific antibody AK112 (Ivonescimab) further enhances treatment efficacy.Methods and analysis This is a single-centre, prospective, phase II trial using Simon’s two-stage design to evaluate the efficacy and safety of neoadjuvant SBRT combined with Ivonescimab and chemotherapy. A total of 50 patients will be enrolled. The primary endpoint is pCR. Secondary endpoints include objective response rate, disease control rate, Residual Cancer Burden Index, 12-month event-free survival, safety and quality of life. Exploratory endpoints include six-point minimal residual disease (MRD) assessment. Data will be analysed using the Kaplan-Meier method and one-sided exact binomial test (alpha=0.05).Ethics and dissemination This study has been approved by the ethics committee of Hubei Cancer Hospital (Approval No.: LCKY2024011). Results will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT06402435.

BACKGROUND:The role of Forkhead Box D2 (FOXD2) in head and neck squamous cell carcinoma (HNSC) has never been studied. OBJECTIVES:Our object was to explore the role of FOXD2 in HNSC. METHODS:Clinical data for patients with HNSC was obtained from TCGA. Our study examined the atypical expression of FOXD2 in both HNSC and pan-cancer, along with its diagnostic and prognostic implications, as well as the association between FOXD2 expression and clinical characteristics, immune infiltration, immune checkpoint genes, and MSI. Gene set enrichment analysis (GESA) was used to investigate the potential regulation network of FOXD2 in HNSC. We analyze the genomic alterations of FOXD2 in HNSC. GSE13397 and qRT-PCR were used for the validation of FOXD2 expression. RESULTS:FOXD2 was aberrantly expressed in 24 tumors. FOXD2 was significantly up-regulated in HNSC compared to normal head and neck tissue (p < 0.001). High FOXD2 expression was associated with the histologic grade of the patient with HNSC (p < 0.001), lymphovascular infiltration (p = 0.002) and lymph node neck dissection (p = 0.002). In HNSC, an autonomous correlation between FOXD2 expression and OS was observed (HR: 1.36; 95% CI: 1.04-1.78; p = 0.026). FOXD2 was associated with the neuronal system, neuroactive ligand-receptor interaction, and retinoblastoma gene in cancer. FOXD2 was associated with immune infiltration, immune checkpoints, and MSI. The somatic mutation rate of FOXD2 in HNSC was 0.2%. FOXD2 was significantly up-regulated in HNSC cell lines. CONCLUSION:Our findings suggest that FOXD2 has the potential to serve as a prognostic biomarker and immunotherapeutic target for individuals with HNSC.

Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of homeobox (HOX) genes, underlying mechanisms remain elusive. Here, we report that the Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated mixed-lineage leukemia 1 (MLL1) recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes. HoxBlinc depletion in NUP98 fusion- driven leukemia impaired HoxBlinc binding, TAD integrity, MLL1 recruitment, and the MLL1-driven chromatin signature within HoxBlinc-defined TADs in a CCCTC-binding factor-independent (CTCF-independent) manner, leading to inhibited homeotic/ leukemic oncogenes that mitigated NUP98 fusion-driven leukemogenesis in xenografted mouse models. Mechanistically, HoxBlinc overexpression in the mouse hematopoietic compartment induced leukemias resembling those in NUP98-PHF23- knockin (KI) mice via enhancement of HoxBlinc chromatin binding, TAD formation, and Hox gene aberration, leading to expansion of hematopoietic stem and progenitor cell and myeloid/lymphoid cell subpopulations. Thus, our studies reveal a CTCF-independent role of HoxBlinc in leukemic TAD organization and oncogene-regulatory networks.

Combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) improves survival in stage III non-small cell lung cancer (NSCLC), though immune-related adverse events (irAEs) require vigilant management. Emerging evidence suggests multi-organ irAEs may correlate with favorable outcomes. We report a case of unresectable stage IIIA NSCLC achieving sustained partial response (PR) with progression-free survival (PFS) exceeding 42 months after one cycle of pembrolizumab-chemotherapy followed by sequential thoracic RT (50 Gy/25 fractions). Severe multi-organ irAEs (muscular, cardiovascular, respiratory, hematologic) developed but were effectively managed with corticosteroid-based therapy. Remarkably, durable tumor control persisted despite suboptimal therapeutic dosing and early systemic treatment discontinuation. This case demonstrates that RT-ICI synergy can induce robust systemic antitumor immunity even with dose-reduced RT, while severe multi-system irAEs may signal favorable prognosis. These findings support optimizing RT parameters (eg, dose de-escalation, target volume refinement) as a viable approach in the immunotherapy era.

Background and aims:Patients with ulcerative colitis (UC) and PR3-ANCA positivity often show a poor response to infliximab (IFX). Our objective was to compare the effectiveness and safety of rituximab (RTX) and IFX in moderately-to-severely active PR3-ANCA positive (PR3-ANCA+) UC patients. This study represents the first exploration of biomarker-guided therapy (PR3-ANCA+) in moderately-severely active UC, aiming to generate hypothesis-driven evidence for future randomized trials. Methods:This retrospective, multicenter, real-world study focused on a rare biomarker-defined subgroup (PR3-ANCA + UC) and was conducted across three medical centers in Hubei, China. Moderately to severely active UC patients with PR3-ANCA+ were assigned to the RTX group (n = 12) and the IFX group (n = 26) based on biological therapy received. Endpoints at week 22 included clinical remission (primary), clinical response, endoscopic response, improvement, and remission. Safety endpoints centered on opportunistic infections and drug-related adverse events. Inverse probability of treatment weighting (IPTW) and multifactorial logistic regression analysis (MLRS) were used to reduce confounding effects. Results:Pre-IPTW, compared with IFX, RTX significantly increased the rates of clinical remission, clinical response, endoscopic response, endoscopic improvement, and endoscopic remission by 60.25% (95%CI: 33.68%-86.82%, P < 0.001), 34.62% (95%CI: 16.33%-52.91%, P = 0.020), 65.38% (95%CI: 45.15%-85.61%, P < 0.001), 38.46% (95%CI: 10.65%-66.27%, P = 0.010), and 65.38% (95%CI: 45.15%-85.61%, P < 0.001), respectively. After IPTW, RTX remained associated with significantly higher rates of the above outcomes versus IFX, with increases of 53.68% (95%CI: 35.26%-72.10%, P = 0.012), 33.90% (95%CI: 16.52%-51.28%, P = 0.002), 62.71% (95%CI: 46.35%-79.07%, P < 0.001), 46.61% (95%CI: 26.83%-66.39%, P = 0.024), and 62.71% (95%CI: 46.35%-79.07%, P < 0.001), respectively. In MLRS, RTX was associated with higher odds of week-22 clinical remission compared with IFX, with consistent results before and after IPTW [pre-IPTW: OR = 31.022 (2.911-970.983), P = 0.010; post-IPTW: OR = 47.692 (4.077-1,418.298), P = 0.007]. Additionally, for every 50% reduction in PR3-ANCA levels, the odds ratio (OR) for clinical remission was 7.583 (95%CI: 1.648-34.903). Furthermore, this conclusion remained robust after adjusting for confounding factors. For safety endpoints, no RTX patients had elevated tuberculosis interferon tests, while 2 IFX patients (7.69%) did. In addition, no HBV reactivation or infection occurred in either group. Mean IgG levels remained stable in RTX-treated patients (11.50 ± 3.59 vs. 10.84 ± 1.48, P = 0.569). Conclusion:In moderately to severely active UC patients with PR3-ANCA+, RTX showed better effectiveness than infliximab (IFX), with a similar safety profile.

Objectives Brain metastases (BMs) are commonly categorized into cystic and solid. However, the difference in the prognosis of patients with either cystic or solid BMs following radiotherapy remains poorly understood. We used a retrospective design to elucidate the disparities in survival between these two patient groups undergoing radiotherapy and to identify factors influencing the overall survival (OS) of patients with BMs. Methods This retrospective study encompasses 212 patients diagnosed with BMs. We meticulously analyzed the clinical characteristics, radiation therapy modalities, and risk factors influencing the OS among these patients, categorized by BMs type, post-brain radiation therapy. Results A statistically significant difference in mOS was observed between the two cohorts (Solid vs Cystic: 23.1 vs 14.6 months). Subgroup analysis unveiled distinctions in mOS, particularly in patients with EGFR-mutant lung adenocarcinoma (Solid vs Cystic: 23.1 vs 6.43 months). The volume of BMs and the biological effective dose (BED) emerged as significantly prognostic factors for patients with cystic BMs. For patients with solid BMs, fraction dose, BED, and the number of BMs were identified as independent prognostic factors for survival. Conclusion Brain radiotherapy shows superior survival benefits for lung cancer patients with solid BMs compared to those with cystic BMs, particularly in EGFR-mutant lung cancer. In particular, patients receiving BED ≥60 Gy have a more favorable prognosis than those receiving BED <60 Gy, regardless of the type of BM (solid or cystic) in lung cancer.

Background Pediatric myelodysplastic syndromes (MDS) are rare disorders with an unrevealed pathogenesis. Our aim is to explore the role of genetic factors in the pathogenesis of MDS in children with different outcomes and to discover the correlation between genetic features and clinical outcomes as well as disease characteristics. Methods We conducted an analysis of archived genetic data from 26 patients diagnosed with pediatric MDS at our institution between 2015 and 2021, examining the association between different genetic characteristics and clinical manifestations as well as prognosis. Additionally, We presented three cases with distinct genetic background and outcomes as examples to elaborate the role of genetic factors in pediatric MDS with different prognoses. Results Genetic variations were detected in 13 out of the 26 patients, including 8 patients with co-occurrence of somatic and germline mutations (CSGMs) and 5 patients with somatic mutations alone. Our analysis revealed that advanced MDS (4/8, 50% vs. 1/5, 20% and 4/11, 36.4%), PD (3/8, 37.5% vs. 1/5, 20% and 1/11 9.1%), and TD (6/8, 75% vs. 2/5, 40% and 2/11, 18.2%) were more common in patients with CSGMs than those with somatic mutations alone or without any mutations. We also found out in our study that 8 patients with CSGMs had evidently different clinical outcomes, and we presented 3 of them as examples for elaboration. Case 1 with germline and somatic mutations of unknown significance had a relatively slow disease course and a good prognosis. Case 2 with compound heterozygous germline SBDS variants and somatic mutations like del20q had a stable disease course and a reversed outcome. Case 3 with a germline GATA2 variant and somatic mutations including − 7 had a rapidly progressive disease course and a worst prognosis. Conclusion Our findings indicate that genetic background of pediatric MDS is closely linked with disease characteristics as well as outcomes and that CSGMs may lead to disease progression. It should be emphasized that the interaction between certain germline variants and somatic mutations, such as SBDS and del20q, may result in hematopoietic stem cell adaptation (improved hematopoiesis) and reversed clinical outcomes, which can facilitate the development of targeted therapy.

Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.

Objective: Monitoring the disease status of Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. Method: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. Results: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with reelevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. Conclusion: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function. (c) 2024 Published by Elsevier Editora Ltda. on behalf of Sociedade Brasileira de Pediatria. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction: Lung cancer remains the most common malignancy and the leading cancer-related death among the elderly in China, which deserves more research attention. Immunotherapy combined with platinum-based doublet chemotherapy has been approved as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients who are devoid of specific gene mutations or fusions. Given that patients with NSCLC over the age of 65 typically exhibit declining organ function and physical condition, they often showed reduced tolerance for this rigorous treatment regimen. However, the KEYNOTE-042 study illuminated a promising pathway: in patients testing positive for programmed deathligand 1 (PD-L1), immunotherapy alone has demonstrated a superior overall survival (OS) compared to platinum-based doublet chemotherapy. This suggests that moderating the intensity of chemotherapy and prioritizing immunotherapy may be a gentler alternative in elderly demographic. Patients and Methods: This multicenter phase II clinical trial named UNICORN aimed to enroll 49 patients aged 65 and older, utilizing paclitaxel or nab-paclitaxel for those with squamous NSCLC, and pemetrexed for those diagnosed with lung adenocarcinoma. The treatment protocol entails 4 cycles of serplulimab plus chemotherapy followed by an extended regimen of serplulimab maintenance, spanning a total of 35 cycles. Primary endpoints of this study are progression-free survival (PFS), disease control rate (DCR) and the secondary endpoints are OS, objective control rate (ORR) and safety metrics. Conclusion: This is the first study to evaluate the efficacy and safety of serplulimab combined with either paclitaxel or pemetrexed in elderly treatment-na & iuml;ve patients with stage IV NSCLC whose PD-L1 are positive.

Hepatocellular carcinoma (HCC) remains a formidable oncological challenge, calling for innovative therapeutic strategies to improve patient outcomes. MicroRNAs have emerged as key regulators in cancer, and miR-3682-3p shows potential as a diagnostic and prognostic biomarker in HCC. We conducted a comprehensive study to uncover its role in HCC biology, revealing dysregulation and clinical associations. Target gene analysis provided insights into potential molecular mechanisms. Moreover, we explored its impact on the tumor microenvironment, immune cell infiltration, and therapy responses. Our findings highlight miR-3682-3p as a promising candidate for further investigations and potential therapeutic strategies in HCC management.

G -rich sequences in DNA and RNA tend to fold into stable secondary structures called G-quadruplexes. Except for the telomere region, G-quadruplex-forming sequences are widely present in gene promoters and have been implicated in transcriptional regulation. Single nucleotide polymorphisms (SNPs) can disrupt the G-quadruplex structure of a gene promoter. In this study, we confirmed the promoter of HSPB2, a cancer -related gene, tends to form an unusual DNA secondary structure. The dual luciferase assay revealed that the SNP rs2234704 in the HSPB2 promoter with a single G > A mutation increased the transcriptional activity of the HSPB2 promoter. Circular dichroism and native PAGE revealed that the G -rich strand of the DNA in this promoter preferred to form a parallel G-quadruplex, which could be destabilized by the SNP rs2234704 (G > A) mutation. Furthermore, we found that the SNP rs2234704 (G > A) greatly increased and influenced the overexpression of HSPB2 in breast cancer samples. These results suggest SNP rs2234704 (G > A) may play a role in the occurrence of breast cancer by destroying the Gquadruplex structure and promoting the expression of HSPB2.

e14609 Background: Hypofractionated radiotherapy (HFRT) of the primary tumor can induce abscopal effects in metastatic cancer, which could be enhanced by adding PD-1 immunotherapy (IO) and low-dose radiotherapy (LDRT) of distant disease. However, this strategy remains with suboptimal efficacy. Translational research has shown that LDRT primarily modulates the immune microenvironment of tumors in the irradiated area, a mechanism shared by anti-angiogenic therapy (AAT). Therefore, this study aimed to compare the efficacy (abscopal responses and cytokine levels in the tumor microenvironment) between HFRT+IO+AAT and HFRT+IO+LDRT. Methods: Bilateral mouse tumor models were divided into seven groups for various treatments (Table 1). After treatment, blood and tumor samples of mice were collected for analysis. We evaluated clinical effects of HFRT+IO+AAT in 4 patients with unirradiated lung metastases in a currently-accruing phase Ib study of stereotactic body radiotherapy (SBRT) plus anlotinib (AAT) with or without toripalimab (PD-1 IO) in driver mutation-negative non-small cell lung cancer (NCT05021328). Results: The results of animal studies are shown in Table 1. HFRT to the primary tumor combined with AAT and IO enhanced the abscopal response in secondary tumor compared to HFRT, HFRT+IO, HFRT+AAT, IO+AAT, as well as HFRT+LDRT+IO. The most noteworthy secondary tumor control was observed in mice receiving HFRT+IO+AAT. The enhanced abscopal responses were associated with increased infiltration of CD8+ effector T cells, increased expression of IFN-γ and levels of TNF-α. From the prospective trial population, 4 unirradiated lung lesions in the HFRT+IO+AAT cohort decreased by an average of 48% in size (n=3 partial response, n=1 stable disease). No grade 3 treatment-related toxicity was observed. Conclusions: HFRT+IO+AAT is a promising therapeutic combination that may optimize abscopal responses, potentially even further than HFRT+LDRT+IO. This new “triple therapy” was safe and efficacious in patients and deserves further study. [Table: see text]

DS GPA and Lung-mol GPA are prognostic tools for brain metastases based on a series of clinical trial data. However, the prognostic value of DS GPA and Lung-mol GPA for the survival of ALK-positive non-small-cell lung cancer (NSCLC) patients with brain metastases is not yet know.

Non-small cell lung cancer (NSCLC) is the most common tumor that metastasizes to the brain. It is now accepted that the successful colonization and growth of tumor cells are determined by the interaction between tumor cells and the tumor microenvironment (TME). Microglia, brain innate immune cells, have been reported to play a vital role in the establishment of brain metastases. As essential mediators of intercellular communications, tumor-derived exosomes have an important role in the pathogenesis and progression of cancer by transferring their cargos to specific recipient cells. The crosstalk between microglia and tumor-derived exosomes has been extensively described. However, it is still unclear whether metastatic NSCLC cells secret exosomes to microglia and regulate the microglial functions. Here, our results showed that microglia aggregated in the brain metastatic sites. Meanwhile, microglia could take up the exosomes derived from NSCLC cells, leading to alterations of microglial morphology and increased proliferation, phagocytosis, and release of inflammatory cytokines including interleukin-6, interleukin-8, and CXCL1. Further investigation indicated that miR1246 was the most enriched microRNA in NSCLC-derived exosomes and mediated the partial effects of exosomes on microglia. Notably, miR1246 was also upregulated in the plasmatic exosomes of NSCLC patients. These results offer a new insight into the impact of NSCLC-derived exosomes on microglia and provide a new potential biomarker for diagnosing NSCLC.