The immune system has devised various receptors to fine tune the immune response. Among them, Inhibitory receptors (IR) comprise a broad spectrum of receptors that contain either immunoreceptor tyrosine-based inhibition motif (ITIM) or immunoreceptor tyrosine-based activation motif under inhibitory mode (ITAMi). Lymphocytes or myeloid cells express different IRs, therefore the action of these receptors is critical in maintaining immunity. Upon ligands engagement, the ITI/ITA motif inside the inhibitory receptors becomes phosphorylated, thus allowing them to recruit different phosphatases and starting a signaling cascade that ultimately dampens immune response.

Genetic models as well as studies with agonist or antagonist molecules have proven how IRs modulate inflammatory or cancer immunity. Studies using knockout mice have shown that the absence of IRs often leads to exacerbated immune response and inflammation. Correspondingly, there is a boost in anti-tumor immunity. In cancer, the treatment with antagonists of IRs (e.g. CTLA4, PD1) or their ligands (PDL1) can remove the immunological brakes that impede immune responses against tumors and have thus provided positive clinical outcomes in some patients. Invading pathogens have also been demonstrated to opportunistically override immunity by engaging IRs as entry receptors and/or altering immune response in different cell types. Therefore, since inhibitory receptors are emerging as promising targets to modulate immune response in cancer, the study of drugs and therapeutic modalities targeting IRs are of crucial importance.

In this Research Topic, we aim to explore recent cutting-edge research covering the broad field of the role of IRs in immune response within inflammation and cancer. We welcome the submission of Original Research articles, Reviews, Methods, Clinical Trials and Perspectives focusing on the following subtopics:

1- Expression of IRs and correlated pathways in health and diseased tissues
2- Modulation of IRs in inflammatory diseases
3- Immunological outcomes of clinical trials and mechanisms of tumor resistance targeting IRs

Topic Editor Dr. Monteiro is the co-founder of Inatherys.
Topic Editor Dr. Zarrin declare no conflict of interest with regard to the Research Topic theme.

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