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This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.68Ga labeled FAPI is the current standard for FAPI-PET, but its batch activity is limited. [18F]AlF-NOTA-FAPI-04 is a promising alternative combining the advantages of a chelator-based radiolabeling method with the unique properties of fluorine-18. The objective of this study was to develop a quick automatic method for synthesis of [18F]AlF-NOTA-FAPI-04 using a AllinOne synthesis system, and perform PET imaging with [18F]AlF-NOTA-FAPI-04 on patients. [18F]AlF-NOTA-FAPI-04 was produced, and its quality control was conducted by HPLC equipped with a radioactive detector. [18F]AlF-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice (n = 3) and 4T1 breast cancer models (n = 3) to determine its biodistribution. Then [18F]AlF-NOTA-FAPI-04 and 18F-fluorodeoxyglucose (FDG) PET/CT imaging were performed in an invasive ductal carcinoma patient (female, 54 years old). The synthesis time of [18F]AlF-NOTA-FAPI-04 was about 25 min, and the radiochemical yield was 26.4 ± 1.5% (attenuation correction, n = 10). The radiochemical purity was above 99.0% and was above 98.0% after 6 h. The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was 49.41 ± 3.19 GBq/μmol. PET/CT imaging in mice showed that physiological uptake of [18F]AlF-NOTA-FAPI-04 was mainly in the biliary system and bladder, and [18F]AlF-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that [18F]AlF-NOTA-FAPI-04 obtained high tumor background ratio (TBR) value of 8.44 in segment V and VI, while TBR value was 2.55 by 18F-FDG. [18F]AlF-NOTA-FAPI-04 could be synthesized with high radiochemical yield and batch production by AllinOne module and show excellent diagnosis performance in cancer patients.Introduction Tumor immune microenvironment (TIME) promotes immune escape, allowing for tumor progression and metastasis. In spite of the current evidence of the complicated role of immune cells in promoting or suppressing cancer progression, the heterogeneity of TIME according to the tumor site has been scarcely investigated. Here, we analyzed transcriptomic profiles of metastatic breast cancer to understand how TIME varies according to tumor sites. Methods Two gene expression datasets from metastatic breast cancer of various sites and a single-cell RNA sequencing dataset of primary breast cancer and metastatic lymph nodes were analyzed. The immune cell-type enrichment of each tumor was estimated. Immune cell types were identified by clustering analysis, and the proportions of cell types in TIME were assessed according to the tumor site. Results Metastatic bone lesions showed more neutrophils than breast lesions. Tumors clustered according to immune cell type were significantly associated with tumor site. In single-cell analyses, the TIMEs of metastatic lymph nodes showed fewer macrophages than those of primary tumors. Differentially expressed gene signatures in the primary tumor and metastatic lymph nodes were associated with macrophage activation. Conclusion We conclude that metastatic sites show variable enrichment patterns of immune cells, and that the TIME of metastatic lesions should be considered in precise immuno-oncology treatments.Myeloid-derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment. Evidence has shown differences in the functions and fates of MDSCs in the tumor tissue and the periphery. However, the exact mechanism that regulates MDSC function has not been completely clarified. In this study, we performed RNA sequencing of MDSCs derived from the spleen and tumor. Based on the results of our RNA-seq analysis, mitogen-activated protein kinases (MAPK) were significantly increased in tumor polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Subsequently, 3 major MAPK pathways, including extracellular signal-regulated protein kinases (ERK), p38 and c-Jun NH2-terminal kinases (JNK), were studied to analyze the role of MAPKs in MDSCs. The ERK 1/2 inhibitor SCH772984 and the JNK inhibitor SP600125 significantly increased the apoptosis of both PMN-MDSCs and M-MDSCs in vitro. In addition, SCH772984 exerted a strong effect on inhibiting tumor growth. The flow cytometry analysis showed significant increases in the ratio of M1M2 tumor-associated macrophages, meanwhile the number of CD4+, CD8+, CD4+CD69+ and CD8+CD69+ lymphocytes were increased after SCH772984 treatment. Our findings established the effect of MAPKs on the tumor microenvironment via MDSCs and may facilitate the development of new antitumor strategies.Limited data reported the synergistic anti-tumor effect of anti-PD-1 (programmed death 1) therapy and radiotherapy on melanoma BM (brain metastasis). And the efficacy in the Chinese population is unclear. This study aimed to evaluate the efficacy of anti-PD-1 therapy and radiotherapy in Chinese melanoma patients with BM. We retrospectively reviewed 96 consecutive melanoma patients with BM treated at Sun Yat-Sen University Cancer Center. Patient demographics, BM characteristics and treatment details were carefully collected. The intracranial PFS (progression free survival) and OS (overall survival) were estimated using the Kaplan-Meier method. Twenty-five patients were treated with anti-PD-1 therapy and radiotherapy. Eighteen (72.0%) patients had SBRT (stereotactic body radiation therapy) or SRS (stereotactic radiosurgery) for BM, 1 (4.0%) patient had WBRT (whole brain radiation therapy), 6 (24.0%) patients had SBRT/SRS and WBRT. The median treatment period of anti-PD-1 therapy was 10.77 months. Objective intracranial response was observed in 15 (60%) patients, and 5 (20%) patients achieved CR (complete response). After a median follow-up of 16 months, 11 (44%) patients experienced intracranial PD (progressive disease), and 15 (60%) patients died. selleck chemicals llc The median intracranial PFS and OS were 10.73 months (range, 1.67-38.83 months) and 15.87 months (range, 2.47-41.50 months), respectively. The 1-year intracranial PFS and OS were 61.9% (95% CI, 44.1-86.9%) and 62.5% (95%CI, 45.8-85.2%), respectively. Patients with BM can benefit from a combination of anti-PD-1 therapy and radiotherapy. It merits further investigation in melanoma patients with BM.