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The impact of microbiota on PD-1/PD-L1 inhibitor therapy outcomes: A focus on solid tumors
Sajad Najafi1, Jamal Majidpoor2, Keywan Mortezaee3
1Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in the last decade. Among various checkpoints identified so far, interaction between programmed death-1 (PD-1) with programmed death ligand 1 (PD-L1) and their targeting using human monoclonal antibodies has attracted the most attention and is considered as the most prominent treatment with the best clinical outcomes. Accumulating evidence is the witness for the impact of gut microbiota on clinical responses and ICI efficacy. Specific bacterial species are identified in fecal specimens of cancer patients responding to the anti-PD-(L)1 immunotherapy, while non-responders demonstrate high abundance of other bacterial sources. Thus, the composition of gut microbiota may suggest potential biomarker in identification of patients with the best responses to immunotherapy. Notably, fecal microbial transplantation (FMT) from responders to non-responders has shown hopeful results in improving clinical outcomes and overcoming resistance to ICIs. Additionally, some bacterial components, such as the use of antibiotics and probiotic supplements have been shown to affect the efficacy of ICIs treatment. However, employment of these findings requires further investigations and precise understanding of the impact of gut microbiota on the host's immune responses. In the current review, we aim to discuss the roles of PD-1/PD-L1 checkpoint pathway, their therapeutic significance, and the impact of gut microbiota/products on the PD-1/PD-L1 immunotherapy outcomes.
Insights
Gut microbiota composition impacts cancer immunotherapy effectiveness. Fecal microbial transplantation from responders to non-responders shows promise in improving outcomes and overcoming resistance to programmed death-1 (PD-1) / programmed death ligand 1 (PD-L1) therapies.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Immune checkpoint inhibitors (ICIs), particularly targeting the programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) pathway, have transformed cancer treatment.
- Emerging evidence highlights the significant influence of gut microbiota composition on patient responses and the efficacy of ICI therapy.
- Distinct bacterial species are associated with response or non-response to anti-PD-(L)1 immunotherapy in cancer patients.
Purpose of the Study:
- To review the roles of the PD-1/PD-L1 checkpoint pathway in cancer therapy.
- To discuss the therapeutic significance of targeting the PD-1/PD-L1 axis.
- To explore the impact of gut microbiota and its products on PD-1/PD-L1 immunotherapy outcomes.
Main Methods:
- Literature review of studies investigating the PD-1/PD-L1 pathway in cancer.
- Analysis of research on the gut microbiome's influence on ICI efficacy.
- Examination of studies involving fecal microbial transplantation (FMT) and its effect on immunotherapy response.
Main Results:
- Specific gut bacterial species correlate with patient response to anti-PD-(L)1 immunotherapy.
- Fecal microbial transplantation from responding patients to non-responding patients has demonstrated potential in improving clinical outcomes and overcoming resistance.
- Factors like antibiotic use and probiotic supplementation can modulate ICI efficacy.
Conclusions:
- Gut microbiota composition may serve as a predictive biomarker for immunotherapy response.
- Further research is needed to precisely understand the mechanisms by which gut microbiota influences host immune responses to ICIs.
- Targeting the gut microbiome presents a potential strategy to enhance the effectiveness of PD-1/PD-L1 based cancer immunotherapies.
