Thread by @microbeminded2

1/ Cool! But a growing # of studies show tumors arn't sterile and harbor communities of bacterial, viral + fungal organisms. Many are intracellular pathogens who’s proteins/metabolites can modulate tumor gene expression and/or viruses that directly integrate into the tumor genome

2/ This team analyzed the PCAWG Consortium datasets and found viruses in 382 genome/68 transcriptome datasets. They noted high prevalence of EBV, HPVs, AAVs, + high levels endogenous retrovirus expression linked to worse survival in kidney cancer patients: biorxiv.org/content/10.110…

3/ Then consider studies like this, which identified a distinct + abundant pancreatic bacterial microbiome associated w/ progressive pancreatic cancer. In mice, this microbiome drove oncogenesis by suppressing macrophage differentiation + T cell activity: cancerdiscovery.aacrjournals.org/content/early/…

4/ Or this pancreatic tumor microbiome study, which found that differences in tumor bacterial content were associated with the metabolic environment (eg: long-term survivor cases had enrichment in pathways related to metabolism of amino acids lipids etc): cell.com/cell/pdf/S0092…

5/ Or this study which found that pathogenic fungi like Malassezia can promote pancreatic oncogenesis, in part by driving the complement cascade via activation of mannose binding lectins that bind the fungal cell wall: nature.com/articles/s4158…

6/ All of the above must be taken into account when creating therapeutics for #cancer - especially CAR T cell immunotherapies and/or "bugs as drugs" #microbiome-derived therapeutics attempting to activate T cells in patients w/ cancers

7/ The presence of pathogens in tumors is almost certainly contributing to the cancer #immunotherapy "cytokine storm syndrome." Activated T cells likely target pathogens in addition to tumor tissue, resulting in significant immunopathlogy (herxheimer) as such pathogens are killed

8/ This can be likened to the Immune Reconstitution Inflammatory Syndrome (IRIS) that occurs when patients w/ #HIV/AIDS are put on antiretroviral drugs that control HIV activity, allowing the immune system to rebound and target co-infectious pathogens: infectiousdiseaseadvisor.com/home/decision-…

9/ I strongly feel that targeting/killing pathogens in the tumor #microbiome before starting CAR T cell immunotherapies wld result in much better survival outcomes, and much less cytokine storm syndrome

10/ For example in one of the pancreatic cancer studies I link to above, targeting the cancer-promoting microbiome with #antibiotics protected against #oncogenesis, reversed intratumoral #immune tolerance, and enabled efficacy for checkpoint-based immunotherapy.