Background: Breast cancer (BC) is the leading cause of cancer‐related death among women. One of the hallmarks of cancer is sustained angiogenesis. YAP/STAT3 may promote angiogenesis and driving BC progression. This study aimed to investigate how YAP/STAT3 affects the immune microenvironment in BC and understand the underlying mechanism.Methods: To establish a tumor‐associated macrophages (TAMs) model, macrophages were cultured in the 4T1 cell culture medium. A BC mouse model was created by injecting 4T1 cells. The expression of YAP, STAT3, p‐STAT3, VEGF, VEGFR‐2, and PD‐L1 was analyzed using immunofluorescence, western blotting, and quantitative real‐time PCR. Flow cytometry was used to identify M1 and M2 macrophages, CD4⁺ T, CD8⁺ T, and Treg cells. Levels of iNOS, IL‐12, IL‐10, TGF‐β, Arg‐1, and CCL‐22 were measured using enzyme‐linked immunosorbent assay. Co‐IP was used to verify whether YAP binds to STAT3. Hematoxylin–eosin staining was used to observe tumor morphology. Cell counting kit‐8 was selected to detect T‐cell proliferation.Results: YAP, STAT3, P‐STAT3, VEGF, VEGFR‐2, and PD‐L1 were highly expressed in BC tissues. The M2/M1 macrophages ratio increased in the TAMs group compared with the control group. Inhibiting of YAP and STAT3 decreased the M2/M1 macrophages ratio. YAP was found to bind with STAT3. T‐cell proliferation was enhanced after YAP inhibition, and overexpression of STAT3 reversed the regulation of YAP on T‐cell proliferation. In animal studies, inhibiting YAP inhibited tumor weight and volume development. After YAP inhibition, inflammatory infiltration, M2/M1 macrophage ratio, and Treg cell ratio declined, while CD8⁺ and CD4⁺ T‐cell ratio increased.Conclusion: In conclusion, this study suggested inhibition of YAP/STAT3 reversed M2 polarization of TAMs and suppressed CD8⁺ T‐cell activity in the BC immune microenvironment. These findings open up new avenues for the development of innovative therapies in the treatment of BC.

Although the efficacy of treatment strategies for cancer have been improving steadily over the past decade, the adverse event profile following such treatments has also become increasingly complex. The present report described the case of a 67‑year‑old male patient with gastric stump carcinoma with liver invasion. The patient was treated with oxaliplatin and capecitabine (CAPEOX regimen) chemotherapy, combined with the programmed cell death protein‑1 (PD‑1) inhibitor tislelizumab. Following treatment, the patient suffered from chills, high fever and facial flushing, followed by shock. Relevant examination results revealed severe multiple organ damage, as well as a significant elevation in IL‑6 and procalcitonin (PCT) levels. Initially, the patient was diagnosed with either immune‑related adverse events (irAEs) associated with cytokine release syndrome caused by tislelizumab or severe bacterial infection. However, when tislelizumab treatment was stopped and the CAPEOX chemotherapy regimen was reapplied, similar symptoms recurred. Following screening, it was finally determined that severe hypersensitivity reaction (HSR) caused by oxaliplatin was the cause underlying these symptoms. A literature review was then performed, which found that severe oxaliplatin‑related HSR is rare, rendering the present case atypical. The present case exhibited no common HSR symptoms, such as cutaneous and respiratory symptoms. However, the patient suffered from serious multiple organ damage, which was misdiagnosed as irAE when oxaliplatin chemotherapy combined with the PD‑1 inhibitor was administered. In addition, this apparent severe oxaliplatin‑related HSR caused a significant increase in PCT levels, which was misdiagnosed as severe bacterial infection and prevented the use of glucocorticoids. This, in turn, aggravated the damage in this patient.

Macrophage M2 polarization plays a pivotal role in breast cancer development. The present study aimed to investigate the interplay of the Leupaxin (LPXN)/HDAC6/EGR2 axis in breast cancer and its impact on macrophage M2 polarization. Our findings indicate that LPXN overexpression in breast cancer tissues correlates with M2 macrophage polarization. To investigate LPXN's potential role, we conducted siRNA-mediated silencing in macrophages. In a breast cancer cell-macrophage co-culture system, LPXN silencing was associated with reduced cancer cell proliferation, decreased M2 polarization markers, and diminished HDAC6 expression. BIOGRD and experimental data suggest a regulatory relationship between LPXN and HDAC6. Notably, HDAC6 inhibition partially reversed the pro-M2 effects of LPXN overexpression. Further mechanistic studies revealed that HDAC6 interacts with EGR2, functioning as its deacetylase and negatively regulating EGR2 expression. EGR2 silencing partially attenuated the anti-M2 effects observed with LPXN knockdown. In murine breast cancer models, LPXN silencing was linked to increased M1 macrophage markers and reduced tumor burden. These findings suggest LPXN may influence breast cancer progression through HDAC6/EGR2-mediated regulation of macrophage polarization. In conclusion, our study demonstrated that the LPXN/HDAC6/EGR2 axis promotes breast cancer progression by augmenting macrophage M2 polarization. Graphical Abstract

Background: Pancreatic cancer remains one of the most lethal malignancies, with a five-year survival rate of merely 8% for exocrine tumors, and conventional chemotherapy offering limited clinical benefit. Nab-paclitaxel plus gemcitabine (AG) is a standard first-line regimen, yet outcomes remain suboptimal. Nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody with a favorable tolerability profile, has demonstrated promising activity in combination with gemcitabine in KRAS wild-type pancreatic cancer. Objective: This study aimed to preliminarily evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and nab-paclitaxel (NTZ-AG) as first-line therapy in patients with locally advanced or metastatic pancreatic cancer. Methods: This single-arm, single-center Phase II prospective study enrolled 16 patients (aged 18–75 years, ECOG PS 0–1) with pathologically confirmed Stage III–IV pancreatic cancer without prior systemic chemotherapy. Patients received nimotuzumab 400 mg (day 1, 3-h infusion), gemcitabine 1,000 mg/m ² (days 1 and 8), and nab-paclitaxel 125 mg/m ² (days 1 and 8) every 21 days for up to 6 cycles. The primary endpoint was objective response rate (ORR), assessed per RECIST v1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), duration of response (DOR), and safety, graded per NCI-CTCAE v5.0. Results: Among 16 evaluable patients, the ORR was 68.75% (11/16; 95% CI: 42.81–87.34%), with no complete responses and 11 partial responses. The disease control rate (DCR) was 100%. Median PFS was 6.0 months (95% CI: 4.06–7.95) and median OS was 12.0 months (95% CI: 8.35–15.66), with one patient achieving an OS of 49 months. Adverse events were predominantly Grade 1–2; no Grade 4 or higher toxicities were observed. Grade 3 events included alopecia (81.2%), nausea (12.5%), and myelosuppression. Conclusion: The NTZ-AG regimen demonstrated meaningful anti-tumor activity and an acceptable safety profile as first-line therapy for unselected advanced pancreatic cancer patients, providing a rational basis for larger randomized controlled trials. Clinical trial registration: This trial was registered at the Chinese Clinical Trial Register (ChiCTR) under the registration number ChiCTR2300072843 having URL https://www.chictr.org.cn/showprojEN.html?proj=198791 .