A multi-omics study by researchers from Japan has found that blood type B (BTB) is associated with reduced immune checkpoint inhibitor (ICI) efficacy in first-line (1L) treatment of head and neck squamous cell carcinoma (HNSCC).
Gut microbiome has been reported to influence ICIs’ efficacy across several tumour types. [Science 2018;359:91-97; Science 2018;359:97-103; Cell Rep Med 2023;4:101251] Since different ABO blood types are associated with varying compositions of the gut, in the present study, the researchers investigated whether blood type may influence response to ICI treatment. [BMC Microbiol 2012;12:94]
“ABO blood type is recognized as a key determinant of gut microbial composition and may affect ICI efficacy through the microbiota,” they wrote. “However, blood type significance in [treatment of] HNSCC remains unclear.” [Ikoma T, et al, ESMO TAT Asia 2026, poster]
The analysis involved data from 120 patients with advanced or recurrent HNSCC who initiated 1L ICI monotherapy and were enrolled in the SCRUM-Japan MONSTAR-SCREEN-1 and -2 monitoring studies of cancer-related genomic alterations and gut microbiome in advanced solid tumours by circulating tumor DNA target panel and 16S rRNA sequencing.
BTB was associated with reduced ICI efficacy, as evidenced by significantly shorter progression-free survival vs non-BTB patients (3.5 vs 4.9 months; p=0.02).
Patients with BTB had decreased abundance of Lactobacillus and Streptococcus mutans vs patients with other blood types. “Given that the gut microbiome modulates anti–PD-1/PD-L1 responses, ABO-related differences in mucosal glycan structures may alter microbiome composition and impair antitumour immunity,” explained the researchers.
Furthermore, patients with BTB showed transcription upregulation of B3GNT3, which encodes a glycan-building enzyme, and an enrichment in the glycosphingolipid biosynthesis pathway. The researchers suggested that alterations in glycan-related pathways, which influence immune recognition, immune evasion and the tumour microenvironment, may further contribute to reduced sensitivity to ICI therapy.
Earlier research by the same group reported significantly poorer overall survival among BTB patients with HNSCC treated with 1L pembrolizumab vs patients with other blood types. [Discov Oncol 2025;16:1302]