Orchestration of immune response by innate lymphoid cell subtype 2 at various tumor microenvironment, a suitable target for cancer immunotherapy

AbstractInnate lymphoid cells are a mixed population of cells and critical regulators of our innate immune system. According to recent scientific literature, tissue resident innate lymphoid cell subtype 2 has been recognized as an important player of type 2 inflammatory responses, involved in different human malignancies like pancreatic, lung, acute myeloid leukemia, gastrointestinal tract cancer, etc. The current reports have revealed that, among the three main ILC sub types, subtype 2 (ILC 2), as the key regulator of initiating the type 2 inflammatory responses at the tumor microenvironment (TME). This activation of ILC-2 is a very important step for the specific downstream functioning of ILC-2. Priming of ILC-2 with different chemokines involves different cytokine secretion from the activated ILC-2 like IL-4, IL-5, IL-13, IL-9 which induce type 2 inflammatory responses involved in the complex interaction with other immune cells like NK cell, Cytotoxic T cell, MDSC and Treg cell. At the initial stage, ILC-2 activation through IL-33 may induce the anti-tumorigenic effect mediated by ILC-2/eosinophil axis. However, it is also evident that PDG2 (Prostaglandin D2)-mediated activation of ILC-2 induces the ILC-2/MDSC immune suppressive pro-tumorigenic niche at the TME. Here, in this review, we have summarized the function of ILC-2 on cancer immunity based on recent scientific work which indicates ILC-2 plays a dual role and orchestrates the immune responses toward type 2 immunity in different cancer settings.Plain Language SummaryCancer is a complex disease where abnormal growth of body cells destroys the normal functions of affected body tissue. It is also one of the leading causes of death worldwide across every continent. There are more than 100 human cancers have been identified until now. Our body has an immune system, which always fights against any harmful agent including cancer cells, which try to invade our immune system and makes us fall ill. Our immune system consists of different specialized cells termed as immune cells which may involve in the direct killing of the cancer cells or it may indirectly help other cells to do it via complex interactions. Innate lymphoid cell or ILC is such type of immune cells of our immune system. Innate lymphoid cell has three main subtypes ILC-1, ILC-2, ILC-3; however, in the context of cancer development and progression, recently, ILC-2 has been recognized as one of the key players. Thus, in this article, we have summarized the activation and various functions of ILC-2 in different cancer settings which conclude that, ILC-2 can be a reasonably good therapeutic target to combat the devastating disease called cancer.Keywords: CytokineILCimmunoregulationinflammation Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis review work was financially supported by the SERB, Department of Science and Technology, Govt. of India [EEQ12019/000153]; ICMR, Govt of India [2021-11421] and DBT BUILDER [BT/INF/22/SP45088/2022].