Abstract
Memory formation, guided by microbial ligands, has been reported for innate immune cells. Epigenetic imprinting plays an important role herein, involving histone modification after pathogen-/danger-associated molecular patterns (PAMPs/DAMPs) recognition by pattern recognition receptors (PRRs). Such “trained immunity” affects not only the nominal target pathogen, yet also non-related targets that may be encountered later in life. The concept of trained innate immunity warrants further exploration in cancer and how these insights can be implemented in immunotherapeutic approaches. In this review, we discuss our current understanding of innate immune memory and we reference new findings in this field, highlighting the observations of trained immunity in monocytic and natural killer cells. We also provide a brief overview of trained immunity in non-immune cells, such as stromal cells and fibroblasts. Finally, we present possible strategies based on trained innate immunity that may help to devise host-directed immunotherapies focusing on cancer, with possible extension to infectious diseases.
Highlights
Monocytic cells including macrophages and dendritic cells (DCs), granulocytes and natural killer (NK) cells, which feature a spectrum of innate immune cells, constitute the quintessential first line of host innate immune defense and appear to undergo epigenetic reprograming during an antimicrobial immune response (Nakayama et al, 2011; Abbas et al, 2014; Saeed et al, 2014; Vono et al, 2017)
Bacille Calmette-Guerín (BCG) induces upregulation of cytokine production, e.g., granulocyte-macrophage colonystimulating factor (GM-CSF), interleukin-15, tumor-necrosis factor (TNF), expression of MHC class II on urothelial cells and activation of APCs associated with clinically relevant host responses (Ikeda et al, 2002; Mitropoulos, 2005; Bisiaux et al, 2009; Pettenati and Ingersoll, 2018)
Clinical studies in Guinea-Bissau have shown that the tuberculosis (TB) vaccine BCG induces cross-protective immune responses among infants in low-resource settings concomitant with a high level of exposure to different infectious agents (Jensen et al, 2015)
Summary
Monocytic cells including macrophages and dendritic cells (DCs), granulocytes and natural killer (NK) cells, which feature a spectrum of innate immune cells, constitute the quintessential first line of host innate immune defense and appear to undergo epigenetic reprograming during an antimicrobial immune response (Nakayama et al, 2011; Abbas et al, 2014; Saeed et al, 2014; Vono et al, 2017). The permanent polarization of certain subsets of these cells – triggered by pathogen-driven inflammation – leads to the development of molecular signatures forming an “immunological matrix.” This “trained immunity” does not resemble immunological memory of adaptive immune cells, i.e., T and B cells, but rather pre-programing of cells that will respond with similar effector molecules to subsequent challenge driven by recognition of. Clinical studies in Guinea-Bissau have shown that the tuberculosis (TB) vaccine BCG induces cross-protective immune responses among infants in low-resource settings concomitant with a high level of exposure to different infectious agents (Jensen et al, 2015) This is clinically significant, since exposure to a variety of infectious agents early in life in countries with high pathogen transmission rates has been postulated to protect against immunological diseases later in adulthood (MacGillivray and Kollmann, 2014), with a crucial role for PAMP-driven shaping of innate immune responses. In this review/viewpoint, we summarize known information concerning trained immunity and discuss relevant observations in view of personalized cancer immunotherapy, on adaptive T-cell responses directed against cancer cells
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