Distinct inactivated bacterial-based immune modulators vary in their therapeutic efficacies for treating disease based on the organ site of pathology

Abstract

Recent developments in understanding how the functional phenotype of the innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: (1) only adaptive immunity confers immunological memory; and, (2) innate immunity lacks specificity. This work describes the observation that innate immune effector cells appear to be differentially recruited to specific pathological sites when mobilized by distinct inactivated bacterial-based stimuli administered subcutaneously. The studies presented suggest that the immune system, upon detecting the first signs of a potential infection by a specific pathogen, tends to direct its resources to the compartment from which that pathogen is most likely originating. The findings from this work puts forth the novel hypothesis that the immunotherapeutic efficacy of a microbial-based stimulus for innate immune mobilization depends on the correct selection of the microbial species used as the stimulant and its relationship to the organ in which the pathology is present.

Cancer immunotherapy with γδ T cells: many paths ahead of us

“…Based on this concept, microbial preparations, called site-specific immunomodulators (SSIs), derived from Klebsiella variicola , Escherichia coli , and Staphylococcus aureus , have been developed and shown in mouse models to have organ-specific effects on the lung, intestine or skin and can stimulate organ-specific antitumor responses. 235 SSIs can also enhance the efficacy of adoptively transferred antitumor T cells by supporting the infiltration of T cells into the tumor microenvironment and increasing tumor immunogenicity. 236 Therefore, it is anticipated that SSIs would provide important additional activation of tumor-reactive γδ T cells in an organ-specific manner, a concept that we believe should be explored in the future.…”

The microbiota is a potential mediator of the crosstalk between γδ T cells and tumors

“…Using two different lung cancer models, researchers found that microbiota-based stimuli that mimicked an acute infection led to a remarkable reduction in tumor burden [53]. Interestingly, Kalyan et al [54] found that subcutaneously injected microbial immunomodulators derived from several inactivated strains had antitumor effects on some specific organs. This result gave rise to an exciting new perspective that organ-specific stimulation of the antitumor activity of γδ T cells can be activated by microbiota that are endogenously located in specific organs.…”