| Autor: |
A.K. Sulit, M. Daigneault, E. Allen-Vercoe, O.K. Silander, B. Hock, J. McKenzie, J. Pearson, F.A. Frizelle, S. Schmeier, R. Purcell |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.04.26.489473 |
| Popis: |
Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. Using CMS subtyping, we aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, focusing onFusobacterium periodonticumandBacteroides fragilisin CMS1, andPorphyromonas asaccharolyticain CMS4. Treatment of peripheral blood mononuclear cells (PBMCs) with LPS isolated from these bacteria showed thatF. periodonticumstimulates cytokine production in PBMCs while bothB. fragilisandP. asaccharolyticahad an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties ofF. periodonticumLPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
