Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity

Abstract

Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICIs), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, which could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.

Repeating late-phase pseudo-progression in a patient with non-small cell lung cancer treated with long-term nivolumab monotherapy; a case report

“…Some previous reports suggest that host immune status and external factors such as COVID-19 vaccinations ( 7 ), corticosteroids ( 8 ), and antibiotics/probiotics ( 9 ) affect anti-cancer immune systems by stimulating or suppressing immune cells. It is well known that diet and lifestyle also affect immune status, these potentially influence the efficacy for ICI therapy ( 10 ). In this patient, we did not change the dose of nivolumab, nor did this patient receive any vaccinations or additional drugs during the three pseudo-progressions.…”

Immunotherapy: remember the host

“…Another host modification that has been shown to be effective in improving IO treatment outcomes is the discontinuation or avoidance of detrimental oral drugs. Use of concomitant antibiotics, corticosteroids, proton pump inhibitors, opioids, and acetaminophen are all associated with poorer IO treatment outcomes ( 21 , 22 ).…”