BACKGROUND: The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses. METHODS: We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed. RESULTS: All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline. CONCLUSIONS Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.
Humans ; Lung Neoplasms/metabolism* ; Interleukin-5/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Retrospective Studies ; Programmed Cell Death 1 Receptor ; Biomarkers ; Immunotherapy ; Disease Progression ; B7-H1 Antigen

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; ErbB Receptors/metabolism* ; Immunotherapy ; Mutation ; B7-H1 Antigen/genetics* ; Protein Kinase Inhibitors/pharmacology* ; Tumor Microenvironment

Humans ; Carcinoma, Hepatocellular/drug therapy* ; Liver Neoplasms/drug therapy* ; Biological Products/therapeutic use* ; B7-H1 Antigen

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans ; Receptors, Antigen, T-Cell, gamma-delta ; Immunotherapy, Adoptive ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy*

OBJECTIVE: To explore the genetic basis for a child with Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB). METHODS: A child with NEDASB who presented at the Third Affiliated Hospital of Zhengzhou University in July 2021 was selected as the subject. Peripheral blood samples of the child and her parents were collected and subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child was found to harbor a heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene, for which both of her parents were of wild type. The variant was predicted as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION The heterozygous c.820_828delinsCTTCA (p.Thr274Leufs*121) variant of the NOVA2 gene probably underlay the disease in this child. Above finding has enriched the spectrum of NOVA2 gene variants and provided a basis for genetic counseling and prenatal diagnosis for this family.
Child ; Female ; Humans ; Pregnancy ; Autistic Disorder/genetics* ; Brain ; Computational Biology ; Genetic Counseling ; Mutation ; Nerve Tissue Proteins/genetics* ; Neuro-Oncological Ventral Antigen ; Neurodevelopmental Disorders ; RNA-Binding Proteins

Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml^-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml^-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.
Male ; Humans ; Prostate/pathology* ; Prostatic Neoplasms/pathology* ; Prostate-Specific Antigen ; Magnetic Resonance Imaging/methods* ; Image-Guided Biopsy/methods* ; Retrospective Studies

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.
Male ; Humans ; Prostate/pathology* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms/diagnostic imaging* ; Biopsy ; Nomograms ; Retrospective Studies

A cross-sectional study was conducted to estimate the age-stratified normal levels and age-related changes in the risk predictors of benign prostatic hyperplasia (BPH) progression. A total of 4706 male participants aged 40 years or older in Zhengzhou (China) were enrolled. The values of the International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), prostate volume (PV), and postvoid residual urine volume (PVR) significantly increased with age. Nonlinear relationships between age and IPSS scores ≥8 (P for nonlinearity = 0.046), PSA level ≥1.6 ng ml^-1, PV ≥31 ml, or PVR ≥39 ml (all P for nonlinearity <0.001) were observed. After the age of 61 years, the risk indicators related to BPH progression were positively correlated with age (odds ratio [OR] >1), regardless of the predictors of the IPSS score, PSA level, PV, or PVR; and the OR values increased gradually. Therefore, after the age of 61 years, the risk predictors related to BPH progression were positively correlated with age.
Humans ; Male ; Prostatic Hyperplasia/diagnosis* ; Prostate-Specific Antigen ; Cross-Sectional Studies ; East Asian People ; Risk Factors

This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml^-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml^-1, 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml^-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml^-1, 4.0-9.9 ng ml^-1, and 2.5-9.9 ng ml^-1, respectively, but not at PSA levels of <2.5 ng ml^-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml^-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml^-1.
Male ; Humans ; Prostate-Specific Antigen ; Prostate ; East Asian People ; Prostatic Neoplasms/diagnosis* ; ROC Curve

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies