Immune checkpoint inhibitors unleash pathogenic immune responses against the microbiota

• DOI: 10.1073/pnas.2200348119
• Publication Date: 2022-06-21T19:03:30Z
• Authors: Zishuo Ian Hu; Verena M. Link; Djalma S. Lima-Ju...; Jérémie Delaleu; Nicolas Bouladoux; Seong-Ji Han; Nicholas Collins; Yasmine Belkaid
• Keywords: Immune checkpoint

Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects unclear etiology and impact virtually all organ systems, with most common being sites colonized microbiota such as skin gastrointestinal tract. Here, we establish a mouse model commensal bacteria-driven irAEs demonstrate that immune inhibition unleashes commensal-specific T cell responses. aberrant responses were dependent on production IL-17 cells induced pathology recapitulated cutaneous inflammation seen in patients treated ICIs. Importantly, unleashed sufficient to perpetuate memory months following cessation treatment. Altogether, established reveal unleash against commensals, long-lasting consequences.