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Growing evidence highlights the pivotal role of RORγt-innate lymphoid cells (ILCs) in the establishment of antitumor immune response and in enhancing tumor sensitivity to immunotherapy. Noteworthy, type 3 ILCs (ILC3s) have been recently acknowledged as an important class of antigen-presenting cells (APCs) in the context of host-microorganism interactions shaping the adaptive immune response in the intestinal mucosa. Although a broad range of mouse models has led to significant progress in untangling the role of ILC3s as APCs, the outcome of major histocompatibility complex (MHC)-dependent ILC-T cell crosstalk in colorectal cancer (CRC) remains underexplored in human. Moreover, expression of MHCII is confined to ILC3 subset, endowed with lymphoid tissue-inducing properties, that adopts tissue-specific fates and functions. Intestinal microbiota could dictate the plasticity of antigen-presenting ILC3s and we here summarize our current understanding of the functions of these cells in both mouse and human CRC discussing the role of microbiota as a key modulator of their tumor-suppressive activity.

Cross-dressing involves the transfer of preformed functional peptide-MHC complexes from the surface of donor cells to recipient cells, such as dendritic cells (DCs). These cross-dressed cells might eventually present the intact, unprocessed peptide-MHC complexes to T lymphocytes. In this review we will discuss some recent findings concerning the intercellular transfer of preformed MHC complexes and the possible mechanisms by which the transfer may occur. We will report evidences showing that both MHC class I and MHC class II functional complexes might be transferred, highlighting the physiological relevance of these cross-dressed cells for the presentation of exogenous antigens to both cytotoxic and helper T lymphocytes., (Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Tertiary lymphoid structures (TLSs) are a common finding in non-small cell lung cancer (NSCLC) and are predictors of favourable clinical outcome. Here we show that NCR(+) innate lymphoid cell (ILC)-3 are present in the lymphoid infiltrate of human NSCLC and are mainly localized at the edge of tumour-associated TLSs. This intra-tumoral lymphocyte subset is endowed with lymphoid tissue-inducing properties and, on activation, produces IL-22, TNF-α, IL-8 and IL-2, and activates endothelial cells. Tumour NCR(+)ILC3 may interact with both lung tumour cells and tumour-associated fibroblasts, resulting in the release of cytokines primarily on engagement of the NKp44-activating receptor. In patients, NCR(+)ILC3 are present in significantly higher amounts in stage I/II NSCLC than in more advanced tumour stages and their presence correlate with the density of intratumoral TLSs. Our results indicate that NCR(+)ILC3 accumulate in human NSCLC tissue and might contribute to the formation of protective tumour-associated TLSs.

Simple Summary: In recent years, growing evidence has suggested that the gut microbiome can significantly influence antitumor immunity, both within and outside the gastrointestinal tract, thereby affecting the efficacy of immune checkpoint inhibitors (ICIs. A link between microbiota composition and response to ICIs has been reported in both mouse and human studies. Gut microbial features depend on a delicate balance of tolerance for commensal microbiota and defense against various potentially pathogenic microbiota orchestrated by host immune system. Type 3 innate lymphoid cells (ILC3s) are a group of tissue-resident innate lymphocytes related to host immune cell–microbiome interactions. They orchestrate immunity, inflammation and tolerance in the intestines and any alterations in their functions can cause gut inflammation, colon cancer and immunotherapy resistance. Type 3 innate lymphoid cells (ILC3s) are primarily tissue-resident cells strategically localized at the intestinal barrier that exhibit the fast-acting responsiveness of classic innate immune cells. Populations of these lymphocytes depend on the transcription factor RAR-related orphan receptor and play a key role in maintaining intestinal homeostasis, keeping host–microbial mutualism in check. Current evidence has indicated a bidirectional relationship between microbiota and ILC3s. While ILC3 function and maintenance in the gut are influenced by commensal microbiota, ILC3s themselves can control immune responses to intestinal microbiota by providing host defense against extracellular bacteria, helping to maintain a diverse microbiota and inducing immune tolerance for commensal bacteria. Thus, ILC3s have been linked to host–microbiota interactions and the loss of their normal activity promotes dysbiosis, chronic inflammation and colon cancer. Furthermore, recent evidence has suggested that a healthy dialog between ILC3s and gut microbes is necessary to support antitumor immunity and response to immune checkpoint inhibitor (ICI) therapy. In this review, we summarize the functional interactions occurring between microbiota and ILC3s in homeostasis, providing an overview of the molecular mechanisms orchestrating these interactions. We focus on how alterations in this interplay promote gut inflammation, colorectal cancer and resistance to therapies with immune check point inhibitors. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are innate lymphocytes which have recently been proposed to play an immunoregulatory role in the pathogenesis and progression of atherosclerosis. Although several studies have evaluated the frequency and the functions of NK cells both in human and in experimental animal models of atherosclerosis, it is yet not clear whether NK cells might behave as protective or pro-atherogenic effectors. Here, we review current knowledge regarding the role of NK cells in atherosclerosis and discuss the potential interactions that might occur in atherosclerotic lesions between NK cells and antigen presenting cells, such as macrophages and dendritic cells. A clearer depiction of the innate immune cell network operating in atherosclerosis might pave the way to novel interesting approaches for the prevention and treatment of this disease. [ABSTRACT FROM AUTHOR]