Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Objective:To deeply analyze differences in characteristics of neurosyphilis between male and female patients with neurosyphilis, as well as between patients with symptomatic neurosyphilis and those with asymptomatic neurosyphilis, and to provide reference for the prevention and control, clinical diagnosis and treatment of neurosyphilis.Methods:A total of 131 inpatients with neurosyphilis were collected from Department of Dermatology and Venereology, the First Affiliated Hospital of Anhui Medical University from June 2015 to December 2019, and their clinical manifestations and laboratory findings were retrospectively analyzed. These patients were grouped according to gender and neurological/psychiatric symptoms. Measurement data were compared by using two-independent-sample t test or Mann-Whitney U test, and enumeration data were compared by using chi-square test and Fisher′s exact test, to analyze differences in clinical characteristics and laboratory indicators between different groups. Results:Among the 131 patients, there were 72 with asymptomatic neurosyphilis (asymptomatic group) and 59 with symptomatic neurosyphilis (symptomatic group). The proportion of patients receiving syphilis treatment was significantly lower in the symptomatic group (10.17%) than in the asymptomatic group (98.61%, OR = 0.002, P < 0.001). The misdiagnosis rate at the first clinical visit was significantly higher in the male patients (50.00%) than in the female patients (24.49%, OR = 3.08, P = 0.004), as well as in the symptomatic patients (89.83%) than in the asymptomatic patients (0, OR = 13.00, P < 0.001). The proportion of symptomatic patients was significantly higher in male patients (57.32%) than in female patients (14.64%, OR = 4.14, P = 0.003). Compared with the female patients, the male patients showed significantly increased positive rates of toluidine red unheated serum test (TRUST) in the cerebrospinal fluid samples (52.44% vs. 26.54%, OR = 3.05, P = 0.004), increased proportions of patients with elevated levels of total protein (> 0.5 g/L) in cerebrospinal fluids (79.27% vs. 59.18%, OR = 2.64, P = 0.01), increased total protein levels in cerebrospinal fluids (0.76 ± 0.41 g/L vs. 0.56 ± 0.25 g/L, P = 0.002), and increased detection rates of brain magnetic resonance imaging abnormalities (72.22% vs. 44.90%, OR = 2.13, P = 0.039). The age at diagnosis of the symptomatic female patients (50.82 ± 9.31 years) was significantly higher than that of the asymptomatic female patients (42.30 ± 12.18 years, P = 0.038). The positive rate of TRUST in the cerebrospinal fluid samples was significantly higher in the patients with symptomatic neurosyphilis (55.93%) than in those with asymptomatic neurosyphilis (31.94%, OR = 2.70, P = 0.006), and so was the total protein level in cerebrospinal fluids (0.79 ± 0.46 g/L vs. 0.60 ± 0.24 g/L, P = 0.003) . Conclusion:The misdiagnosis rate of neurosyphilis is high at the first clinic visit; the condition of male patients is more serious than that of female patients; anti-syphilitic treatment history, gender and age may play some role in the development of neurosyphilis.