Gut Microbiota Potentiates the Effect of Immune Checkpoint Therapy against Cancers

Abstract

Immune checkpoints have been aggressively investigated for anti-cancer immunotherapy. The power of microbiota on the outcome of this immunotherapy has attracted much attention. For example, intestinal microorganisms play a key role in the effectiveness of programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade. Additionally, short-chain fatty acids produced in the gut may modulate anti-CTLA4 and anti-PD1 stimulated immune responses and their anti-tumor efficacy. Enhancing the anti-tumor effects of CTLA4 blockade depends on specific Bacteroides sp. of the gut microbiota, suggesting novel approaches to improve such immunotherapies. However, the molecular mechanism of the immune-potentiation remains largely unknown. Changes in the microbiota are influenced by dietary and environmental factors. Here, we have suggested the molecular mechanism of action regarding the interplay between gut microbiota and the anti-cancer immune system with APRO family proteins, which might contribute to innovative cancer therapy in the future.

Non-Coding RNAs and Gut Microbiota in the Pathogenesis of Cardiac Arrhythmias: The Latest Update

“…This phenomenon has been hypothesized to be related to the action of gut microbiota just on dendritic cells, which are essential to trigger suitable T-cell responses [ 83 ]. Additionally, short-chain fatty acids (SCFAs) formed within the gut microbiota might also modulate those anti-CTLA-4 and anti-PD-1 immune responses as well as their anti-tumor efficacy [ 84 ]. SCFAs are categorized by having fewer than six carbons, such as acetate, propionate, and butyrate, which are mostly produced in the gut as fermentation products.…”

Fatty Acid Metabolites and the Tumor Microenvironment as Potent Regulators of Cancer Stem Cell Signaling

“…Microbial imbalance in the gut, called dysbiosis, is now supposed to be one of the gateways to cancer [ 75 ]. In addition, the gut microbiota may cause increased efficacy and decreased toxicity of current chemotherapy mediators [ 76 ]. The communication between gut microbiota and host cells may indicate a novel research area into potential machinery regulating the efficacy of cancer immunotherapies.…”

“…In particular, host-directed immunomodulation via the gut microbiota appears promising for a successful defense against cancers. Therefore, the gut microbiota might potentiate not only the effect of an immune checkpoint blockade therapy but also of the so-called onco-checkpoints [ 76 ]. Probiotic bacteria may be administered to support cancer treatment.…”

“…Probiotic bacteria may be administered to support cancer treatment. Identifying the relevant supportive mechanisms may provide a promising strategy for probiotic-based dietary therapies, which may be integrated with cancer therapy to improve the outcomes of therapy and patients’ quality of life [ 76 ].…”