Abstract 646: Characteristics of skin microbiome in immune related cutaneous adverse events
Authors: Kraehenbuehl Lukas , Frame John , Taur Ying , Chekalil Sara , Liu Cailian , Goleva Elena , Berdyshev Evgeny , Kern Jeffrey A. , Leung Donald Y. , Wolchok Jedd D. , Lacouture Mario E. , Merghoub Taha 
Published: June 2023

Abstract
Background: Immune-related (ir) cutaneous adverse events (ircAE) frequently complicate immune checkpoint blockade (ICB). Whereas a predictive role for the gut microbiome associated with ir colitis has been identified, a role for the skin microbiome in ircAE has not been explored extensively. In this study we sought to investigate the characteristics of the skin microbiome associated with ircAE.
Methods: Patients developing ircAEs as well as control patients on active ICB without ircAE were prospectively enrolled in an observational cohort study (NCT04283539). Skin microbiome samples were collected using skin tape stripping (STS), followed by shotgun metagenomic sequencing. Clinical, pathological and immunological characterization was conducted for every patient as part of the trial.
Results: 217 samples were available for analysis after shotgun metagenomic sequencing, including 20 from patients on ICB without ircAE, 59 from patients with maculopapular (MPR), 52 from eczematiform (ECZ), 41 from lichenoid and 45 from pruritus on apparently unaffected skin. When assessing similarity of samples using cosine similarity, similarity was stronger within samples from the same patient from affected and unaffected locations or different timepoints, compared to samples of different patients with the same ircAE phenotype (p = 0.025). Samples from patients without ircAE were enriched in anaerobic Eubacteriales (14% mean abundance), whereas samples from ircAE were enriched in Proteobacteriae (30% mean abundance alone) and weakly Bacilli-enhanced (7% mean abundance alone in ircAE, p = 0.041). Furthermore, Staphylococci were more abundant in ircAE samples than in samples from patients without ircAE (p= 0.0328). Similarly, to abundance in the gut being protective of ir colitis, specific Bacterioidetes protective of ir colitis were more abundant in controls than in samples from patients with MPR and ECZ ircAE phenotypes (mean of 3.4% in these ircAE samples, 11.5% mean abundance in controls: p = 0.0231). The proteobacteria/firmicutes ratio, an established marker of dysbiosis in the gut, was also elevated (mean 9.05 vs. 3.77 Proteobacteriae to Firmicutes) in samples from patients with ircAE (MPR/ECZ), when compared to those without ircAE (p = 0.018).
Conclusions: Prospective sampling using STS allows for comprehensive comparative investigation of the skin microbiome of patients developing ircAEs. Microbiotal similarity was strongest within individual patients. Skin of patients treated with ICB without ircAE was enriched in anaerobic bacteria, the microbiota of patients with ircAE was characterized by abundance of Proteobacteriae and Bacilli. Similar to the gut microbiome, Bacterioidetes were more abundant in skin without ircAE. Recruitment of additional patients, as well as adding further ircAE phenotypes will allow for a stronger signal and might allow to differentiate the skin microbiome depending on ircAE phenotypes.
Citation Format: Lukas Kraehenbuehl, John Frame, Ying Taur, Sara Chekalil, Cailian Liu, Elena Goleva, Evgeny Berdyshev, Jeffrey A. Kern, Donald Y. Leung, Jedd D. Wolchok, Mario E. Lacouture, Taha Merghoub. Characteristics of skin microbiome in immune related cutaneous adverse events [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 646.