Reprogramming the tumor microenvironment to improve the efficacy of cancer immunotherapies.

The immunotherapeutic approaches based on checkpoint inhibitors, tumor vaccination, immune cell-based therapy, and cytokines were developed to engage the patient's immune system against cancer and better survival of them. While potent, however, preclinical and clinical data have identified that abnormalities in the tumor microenvironment (TME) can affect the efficacy of immunotherapies in some cancers. It is therefore imperative to develop new therapeutic interventions that will enable to overcome tumor-supportive TME and restrain anti-tumor immunity in patients that acquire resistance to current immunotherapies. Therefore, recognition of the essential nature of the tolerogenic TME may lead to a shift from the immune-suppressive TME to an immune-stimulating phenotype. Here, we review the composition of the TME and its effect on tumor immunoediting and then present how targeted monotherapy or combination therapies can be employed for reprogramming educated TME to improve current immunotherapies outcomes or elucidate potential therapeutic targets.

Association of Tumor Necrosis Factor-α and Myeloperoxidase enzyme with Severe Asthma: A comparative study.

Background: Tumor necrosis factor-alpha (TNF-α) may stimulate airway hyperresponsiveness in asthma, which is also affected by neutrophils activity. The latter can be determined indirectly by evaluating myeloperoxidase (MPO) activity. The insufficient studies that investigated the combined association of serum TNF-α and MPO with asthma was objective of this study. Methods: A case-control study included 110-asthmatics besides 92-controls. All participants underwent venous sampling for TNF-α and MPO immunoassays. A percentage of predicted "forced expiratory volume in one second (FEV1%)", and the "peak expiratory flow rate (PEF/L)" of all participants were verified. The statistical analyses had done using SPSS V-25. The accuracy, specificity, sensitivity, and significance of both biomarkers to distinguish asthma examined "under the ROC-curves". Results: High TNF-α levels observed among the controls(p-0.006), opposing the higher MPO levels among the patients(p-0.00). There were nonsignificant variations of two biomarkers between the treatment groups and nonsignificant correlations of MPO with FEV1 and PEF. There was a significant correlation of MPO with the TNF-α levels of all participants. The TNF-α showed lower sensitivity, specificity, and accuracy to diagnose asthma. There were no MPO differences according to asthma levels. The TNF-α was higher among the severe asthmatics significantly. Discussion: TNF-α may be a contributory particle for neutrophilic inflammation of severe asthma. MPO levels were significantly higher among asthmatics, whereas TNF-α levels were lower. TNF-α levels were higher among those with severe compared to mild/moderate asthma. The MPO level has a significant predictive capacity compared to TNF-α for distinguishing asthma from healthy subjects.