RT Journal Article
SR Electronic
T1 Pairwise Interactions in Adjuvant Combinations Dictate Immune Responses and Inform Cancer Immunotherapy Design
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.11.198879
DO 10.1101/2020.07.11.198879
A1 Surya Pandey
A1 Adam Gruenbaum
A1 Tamara Kanashova
A1 Philipp Mertins
A1 Philippe Cluzel
A1 Nicolas Chevrier
YR 2020
UL http://biorxiv.org/content/early/2020/07/12/2020.07.11.198879.abstract
AB The immune system makes decisions in response to complex combinations of microbial inputs. We do not understand the combinatorial logic that governs how the interplay between higher-order combinations of microbial or adjuvant signals shape immune responses, which hampers the rational design of vaccines and immunotherapies. Here, using in vitro coculture experiments and statistical analyses, we discover a general property for the combinatorial sensing of microbial signals, whereby the effects of triplet combinations of adjuvants on immune responses can be explained by the effects of single and pairwise stimulations. Mechanistically, we find that adjuvant singles and pairs dictate the information signaled by triplets in mouse and human DCs at the levels of transcription, chromatin and protein secretion. Furthermore, we exploit this simplifying property to develop and characterize cell-based immunotherapies using adjuvant combinations with anti-tumor properties in mouse models. We conclude that the processing of complex mixtures of microbial or adjuvant inputs by immune cells is governed by pairwise effects, which will inform the rationale combination of immunomodulatory agents such as adjuvants to manipulate immunity.Competing Interest StatementThe authors have declared no competing interest.