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 immunesuppressive 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.

Background: Bronchial asthma (BrA), recognized lately as an umbrella, covers various subtypes rather than only one disease. Asthma is a chronic inflammation of the airways, in which cytokines could play a crucial role in its pathogenesis. Hence, labors to progress noninvasive markers for asthma had centered through this era. Presently, the fractional exhaled nitric oxide (FeNO), serum C-reactive protein (CRP), and interleukin levels are emerging analytical biomarkers in this field. FeNO is a noninvasive and practical tool even in mild asthma. This study aimed to evaluate the utility of serum IL-1β and CRP together with fractional exhaled nitric oxide in the diagnosis of adult bronchial asthma. Method: The study was a case control, including 150-patients and 100-healthy controls. FeNO tests, measurements of plasma levels IL-1β and HS-CRP had undertaken for all the participants. The statistical data had examined by SPSS (V/27) for Windows. Descriptive data of the variables had compatibly used. A significance lower than or identical to 0.05 had intended. ROC curve examination of FeNO tests, IL-1β, and HS-CRP, to predict asthma from healthy control had applied. Results: there was a significant difference in the FeNo test, HS-CRP levels, and BMI, while no significant difference in all other variables between the groups. The FeNo results correlate positively, though not significantly, with the levels of IL-1β in asthmatic patients (> 0.05). There was a nonsignificant negative correlation between the FeNo results with the level of HSCRP. The accuracy, sensitivity, and specificity of the IL-1β to distinguish asthma were 68.6% and 58% at 95% CI [0.41-0.745], respectively, which was not significant (p>0.05). However, ROC analysis of HS-CRP revealed predictability for asthma patients (p-0.000), with higher accuracy, sensitivity, and specificity: 89.9%, and 68.1% at 95% CI [0.820-0.979], respectively. The FeNo tests revealed highly significant (0.000), high sensitivity, and specific (91% for both) with high 95% CI [0.938-1.000] predictability for asthma. Conclusion: The utility of circulating HS-CRP is more valuable than IL-1β when combined with fractional exhaled nitric oxide in the diagnosis of asthma. Novel biomarkers could improve the precision of this field.