Impact of the microbiome on checkpoint inhibitor treatment in patients with non-small cell lung cancer and melanoma

Abstract

The microbiome is increasingly recognized for its role in multiple aspects of cancer development and treatment, specifically in response to checkpoint inhibitors. While checkpoint inhibitors have revolutionized cancer treatment by producing durable anti-tumor responses, only a minority of patients respond to the available immunotherapy drugs and accurate, sensitive and specific microbiome predictors of response to treatment remain elusive. Additionally, the specific mechanisms linking the microbiome and host immunological responses remain unclear. In this review, we examine the evidence for the gut microbiome's association with anti-tumor responses to checkpoint inhibitors in the treatment of melanoma, non-small cell lung cancer, and renal cell carcinoma. Furthermore, we discuss the current evidence available from murine models seeking to explain the immunological mechanisms that may drive this process. While this work is promising in defining the impact of gut microbiota in cancer treatment, many unanswered questions indicate the need for additional human and experimental studies.

Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC)

“…However, recent studies show that the antibiotic therapy may be associated with reduced therapeutic effects of ICI therapy. Routy et al published data suggesting that antibiotic use within 60 days before treatment initiation is associated with a negative effect on OS in a mixed cohort of NSCLC, urothelial carcinoma and RCC patients [ 41 , 102 ].…”

“…In a follow-up study with a larger population of NSCLC patients, it was observed that antibiotic use within 1 month before immunotherapy was associated with a significantly worse OS [ 42 , 102 ]. These findings are consistent with other results demonstrating that broad spectrum antibiotic therapy within 2 weeks prior to or after ICI use is associated with shorter PFS and a lower response rate [ 43 , 102 ].…”

Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

“…Several parameters influencing the probability of response to ICIs have been identified and recently reviewed elsewhere [ 5 ]. These can be subdivided into features of the tumor genome [ 6 , 7 ], host immune-related traits [ 8 ] and the microbiota [ 9 – 11 ]. These multiple and diverse factors shape the complex interaction of the tumor and the immune system.…”

Airway Microbiota as a Modulator of Lung Cancer

“…However, all patients with cancer do not respond to ICI treatment. Furthermore, recent studies have suggested that some intestinal bacteria are capable of enhancing antitumor immunity and augmenting the effect of ICIs [97][98][99]. A study using a mouse model showed that Bifidobacterium activated dendritic cells, and thereby enhanced antitumor immunity and augmented the antitumor effect of the anti-PD-L1 antibody [97].…”