Lm-LLO-Based Immunotherapies and HPV-Associated Disease

Figure 2

Hypothetical representation of in vivo effects of Lm-LLO-based immunotherapy. Lm-LLO-based immunotherapy evokes a cascade of events in vivo which involves multiple cell types that may (a) regress existing tumors and (b) block tumor reoccurrence. The physiological events associated with these potent therapeutic and prophylactic events include the following: (1) unusually rapid immunological memory consolidation is generated with five-hour post-Listeria-based immunotherapy [41, 42]; (2) promotes bystander effects via activation of cytokines, chemokines, and/or their receptors regulate functions such as leukocytosis, memory, and listeriosis [20]; (3) stimulates synthesis and maturation of immune myeloid cells by stimulating formation of myeloid cells and maturation of dendritic cells [39, 43, 44]; (4) guides heterologous Ag (HPV) processing to generate antigen-specific CD4⁺ and CD8⁺ cells, via MHC class II and I pathways, respectively [34, 43]; (5) reduces Tregs and MDSC only in tumors and diminishes the tumor’s resistance to immune attack by antigen-specific cells [4, 14, 20, 45]; (6) boosts class 1 and 2 arms of adaptive immune response which generates strong cell-based antitumor immunity [9, 24, 30]; (7) chemotaxis and extravasation of activated immune cells is part of an innate immune response, involving the recruitment of nonspecific leukocytes into tumors [34, 46, 47]; (8) PAMP-mediated innate immune stimulation facilitates processing of live Listeria which evokes the essential activity of inflammasomes and innate immunity [48].