Genomic and immune landscape of recurrent and/or metastatic squamous cell carcinoma of the head and neck progressing on anti-PD1 treatment.
(2026) Cancer immunology research — Vol. 14, n° 4, p. 608-624 (2026)
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van der Elst, Athenais 
Herrero-Saboya, Daniel Michon, Lucas Morfouace, Marie Machiels, Jean-Pascal H - et. al.
- Abstract
- Anti-PD1 therapies improve survival in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), but only a minority of patients achieve durable responses. The mechanisms driving resistance to anti-PD1 in SCCHN remain poorly understood. Using the IMMUcan multi-omics workflow, we characterized the molecular and immune profiles of R/M SCCHN progressing on anti-PD1 treatment and compared them to an anti-PD1-naïve cohort. Tumor biopsies from anti-PD1 resistant SCCHN patients exhibited significantly more EGFR and MYCL amplifications, along with increased MYC pathway alterations. Transcriptomic and proteomic analyses revealed that anti-PD1 secondary resistant SCCHN had increased CD8+ T cell infiltration with higher levels of immune exhaustion markers than primary resistant and naïve SCCHN. Additionally, high B2M expression correlated with greater T cell infiltration and improved survival following anti-PD1 therapy. Tumor cell B2M expression was independent of TMB and PD-L1 expression, suggesting that B2M expression could serve as an additional biomarker for anti-PD1 response.
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van der Elst, A., Herrero-Saboya, D., Michon, L., Morfouace, M., Liechti, R., Devanand, P., Schulz, D., Persoons, M., Rusakiewicz, S., Eling, N., Nicolas, P.-A., Robert, M.-S., Tissot, S. R., Daniel, M., Bodenmiller, B., Hong, H. S., Galot, R., Bossi, P., Oliveira, J., et al. (2026). Genomic and immune landscape of recurrent and/or metastatic squamous cell carcinoma of the head and neck progressing on anti-PD1 treatment. Cancer immunology research, 14(4), 608-624. https://doi.org/10.1158/2326-6066.CIR-25-0979 (Original work published 2026)