Hypoxia and programmed cell death-ligand 1 expression in the tumor microenvironment: a review of the effects of hypoxia-induced factor-1 on immunotherapy.

One useful cancer treatment approach is activating the patient's immune response against the tumor. In this regard, immunotherapy (IT) based on immune checkpoint blockers (ICBs) has made great progress in the last two decades. Although ITs are considered a novel approach to cancer treatment and have had good results in preclinical studies, their clinical success has shown that only a small proportion of treated patients (about 20%) benefited from them. Moreover, in highly progressed tumors, almost no acceptable response could be expected. In this regard finding the key molecules that are the main players of tumor immunosuppression might be helpful in overcoming the possible burdens. Hypoxia is one of the main components of the tumor microenvironment (TME), which can create an immunosuppressive microenvironment in various ways. For example, hypoxia is one of the main factors of programmed cell death ligand-1 (PD-L1) upregulation in tumor-infiltrating Myeloid-Derived Suppressor Cells (MDSCs). Therefore, hypoxia can be targeted to increase the efficiency of Anti-PD-L1 IT and has become one of the important issues in cancer treatment strategy. In this review, we described the effect of hypoxia in the TME, on tumor progression and immune responses and the challenges created by it for IT.

Mouse Model of Irritant Contact Dermatitis.

Background: Irritant contact dermatitis is a common inflammatory skin disease characterized by skin barrier dysfunction, eczematous dermatitis, and chronic itching. This disease severely affects the quality of life. Considering that the current treatment approaches are not ideal, more extensive research is needed to develop new treatments. Mainly, a mouse model is needed to investigate the effectiveness of new drugs to treat this disease. Objectives: This study was conducted to create a mouse model of irritant contact dermatitis. Methods: In the current study, we used BALB/c female mice to prepare a mouse model of irritant contact dermatitis. To induce irritant contact dermatitis, we used a dinitrochlorobenzene mixture with acetone/olive oil as an irritant. After 10 days of application, the mouse skin tissue was isolated and examined in terms of histopathology. Results: The introduced protocol created an irritant contact dermatitis model clinically and histopathologically. Conclusions: In the present study, we introduced a new protocol using a mixture of dinitrochlorobenzene and acetone/olive oil to create an irritant contact dermatitis model. Mouse models have been extensively used to discover the complex mechanisms of irritant contact dermatitis and provide a preclinical platform before conducting clinical interventional research on humans to evaluate a new therapeutic approach. However, one should always look for models that cause the least pain and suffering in the animal and simultaneously are simple and reliable for the desired studies. Thus, our protocol is a new approach that can be effective and painless in creating a model of irritant contact dermatitis.