Primary infection enhances neutrophil-mediated host defense by educating HSPCs.

Hematopoietic stem and progenitor cells (HSPCs) can give rise to all kinds of immune cells including neutrophils. Neutrophils are the first line of defense in the innate immune system with a short lifespan, due to which it is well-accepted that neutrophils have no immune memory. However, recent reports showed that the changes in HSPCs induced by primary stimulation could last a long time, which contributes to enhancing response to subsequent infection by generating more monocytes or macrophages equipped with stronger anti-bacterial function. Here, we used the reinfection mice model to reveal that primary infection could improve neutrophil-mediated host defense by training neutrophil progenitors in mammals, providing a new idea to enhance neutrophil number and improve neutrophil functions, which is pretty pivotal for patients with compromised or disordered immunity.

Regulation of ferroptosis-related genes in CD8+ NKT cells and classical monocytes may affect the immunotherapy response after combined treatment in triple negative breast cancer.

BACKGROUND: Drug resistance has led to the failure of immunotherapy in triple negative breast cancer patients. Here we aimed to explore the mechanisms of drug resistance in patients in order to enhance their response to immunotherapy. METHODS: We downloaded publicly available single-cell RNA-sequencing data of peripheral blood mononuclear cells from patients after treatment to investigate the possible mechanisms of drug resistance. The publicly available TCGA transcriptomic data and somatic mutation data were used for further validation. In this study, a series of bioinformatics and machine learning methods were employed. RESULTS: We identified the vital roles of CD8+ NKT cells and classical monocytes in the immunotherapy response of triple-negative breast cancer patients. The proportion of these cell types was significantly increased in group partial response. We also found that downregulation of ferroptosis-related genes regulates the immune pathway. The analysis of scRNA data and TCGA transcriptomic data presented that DUSP1 may play a crucial role in immunotherapy resistance. CONCLUSION: Overall, the composition of the tumor microenvironment affects the immunotherapy response of patients, and DUSP1 may be a potential target for overcoming drug resistance.

Turbulence of glutamine metabolism in pan-cancer prognosis and immune microenvironment.

Introduction: Glutamine is characterized as the nutrient required in tumor cells. The study based on glutamine metabolism aimed to develop a new predictive factor for pan-cancer prognostic and therapeutic analyses and to explore the mechanisms underlying the development of cancer. Methods: The RNA-sequence data retrieved from TCGA, ICGC, GEO, and CGGA databases were applied to train and further validate our signature. Single-cell RNA transcriptome data from GEO were used to investigate the correlation between glutamine metabolism and cell cycle progression. A series of bioinformatics and machine learning approaches were applied to accomplish the statistical analyses in this study. Results: As an individual risk factor, our signature could predict the overall survival (OS) and immunotherapy responses of patients in the pan-cancer analysis. The nomogram model combined several clinicopathological features, provided the GMscore, a readable measurement to clinically predict the probability of OS and improve the predictive capacity of GMscore. While analyzing the correlations between glutamine metabolism and malignant features of the tumor, we observed that the accumulation of TP53 inactivation might underlie glutamine metabolism with cell cycle progression in cancer. Supposedly, CAD and its upstream genes in glutamine metabolism would be potential targets in the therapy of patients with IDH-mutated glioma. Immune infiltration and sensitivity to anti-cancer drugs have been confirmed in the high-risk group. Discussion: In summary, glutamine metabolism is significant to the clinical outcomes of patients with pan-cancer and is tightly associated with several hallmarks of a malignant tumor.