Immune checkpoint inhibitor {51111256}

Shared Reference Notes

• [1.1] [#Cancer] 
• [1.2] [#Antibiotic Therapy] 
  - antibiotic use close to the start of ICI treatment may impair treatment response
• [#Antibiotic Therapy] - decrease in the abundance of #Bifidobacterium members with antibiotics use was associated with impaired response to ICI targeting the programmed cell death protein 1 (anti-PD-1)
• [#Cancer, #Melanoma] - An immune checkpoint inhibitor (ICI)-favorable response was characterized by an intestinal microbiome rich in bacteria such as #Oscillospira sp., #Clostridia UCG-014, #Lachnospiraceae UCG-010 sp., #Prevotella copri, and a decrease in #Sutterella sp., #Lactobacillales, and #Streptococcus sp. - Patients who developed immune-related adverse events (irAEs) had an overall increased microbial diversity and richness, and a stool microbiome depleted in #Agathobacter.
• [#Akkermansia muciniphila] - The most prominent taxa associated with good response to ICI across different #Cancer types are #Phascolarctobacterium, #Bifidobacterium, A. muciniphila and #Rothia.
• - In multiple advanced #Melanoma datasets > #Roseburia spp. associated with good response to ICI
• [1.3] [#Antibiotic Therapy] 
  -Oral antibiotics can disrupt the gut microbiome and antibiotic use close to the start of ICI treatment may impair treatment response
• - increased abundance of #Akkermansia muciniphila, #Phascolarctobacterium, #Bifidobacterium and #Rothia in stool are consistently associated with better response to ICI treatment. - A. muciniphila is also more abundant in stool in patients with higher muscle mass, and muscle mass is a strong positive prognostic marker in #Cancer, including after ICI treatment.
• [1.4] 
  - #Eudoraea and #Desulfonatronospira showed significant increase in patients who benefited from the treatment, suggesting that increasing abundance of these two genera in tumors may improve the outcome of ICB treatment. - #Eudoraea could enhance anti-PD-1 immunotherapy in #Melanoma. - Treatment with #Eudoraea alone or in combination with anti-PD-1 did not result in significant changes in spleen size and body weight. - increases in the percentage of immune cells in the tumor, percentage of CD8+ T cells in the T cells (CD8+/CD3+), and percentage of cytolytic T cells in the CD8+ T cells (GZMB+/CD8+) for the combination of anti-PD-1 and #Eudoraea. - 458 upregulated and 10 downregulated genes in the combination therapy of anti-PD-1 and #Eudoraea vs. anti-PD-1.
• [1.5] [#Bacteroides caccae, #Faecalibacterium prausnitzii, #Prevotella copri, #Streptococcus parasanguinis] 
  - The most distinctive species associated with ICI treatment response were F. prausnitzii, S. parasanguinis, B. caccae, and P. copri,
• [#Bacteroides ovatus, #Blautia obeum] - The most distinctive species associated with ICI non-response were B. obeum and B. ovatus.
• [1.6] [#Antibiotic Therapy] 
  - metabolites from these bacteria drove the downregulation of MAdCAM-1. - MAdCAM-1 typically binds a class of receptors called α4β7 on the surface of regulatory T cells, which have immunosuppressive functions. - Dampening the levels of MAdCAM-1 ultimately directed these immunosuppressive cells to the tumor microenvironment, where their activity worked against immunotherapy
• - In #Cancer patients undergoing immunotherapy, low levels of serum-soluble MAdCAM-1 correlated with intestinal dysbiosis and poor clinical outcomes for renal, bladder, and lung tumors
• [1.7] [#Fecal Microbiota Transplantation] 
  - Comparison of pre- and post-FMT stool samples in Immune checkpoint inhibitors patients with complete responses showed significant increases in alpha diversity and increases in the abundances of #Collinsella and #Bifidobacterium, which were depleted in FMT responders before FMT.
• - Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like #immune-mediated Colitis (IMC).
• [1.8] [#Cancer] [#Antibiotic Therapy] 
  - Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT.
• [1.9] [#Faecalibacterium prausnitzii] 
  - patients receiving ICIs who developed #Colitis had a lower abundance of F. prausnitzii. - F. prausnitzii administration mitigated the exacerbated #Colitis induced by ICIs. - F. prausnitzii enhanced the anti-tumor immunity elicited by ICIs in tumor-bearing mice while abrogating #Colitis. - administration of F. prausnitzii increased gut microbial alpha diversity and modulated the microbial composition, increasing a subset of gut probiotics and decreasing potential gut pathogens. - F. prausnitzii abundance was reduced in mice that developed ICI-associated #Colitis.
• [#Bifidobacterium infantis] - Beneficial Treg effects mediated by B. infantis have also been demonstrated to dampen the side effects of immune checkpoint therapies in a tumor model
• [1.11] 
  - an abundance of #Akkermansia has been associated with a clinical benefit from immune checkpoint inhibitors in patients with non-small cell lung or renal #Cancer
• [1.12] [#Non-small-cell lung cancer] 
  - presence of #Fusobacterium was negatively associated with responsiveness to ICB treatment in NSCLC. - Fuso-high tumors had significantly lower cytotoxic, IFNG, and major histocompatibility complex (MHC) class II gene expression signatures
• [1.13] 
  - resistance is attributable to the activity of #Vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of #Bacteroides fragilis, which positively regulates #Cancer immunity.
• [#Cancer] - mice with increased availability of #Vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies.
• - in humans, #Vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to #Cancer and increased overall survival.

References Notes