Tebentafusp induces systemic immune activation, but tumor immune remodeling remains incompletely validated: a narrative review in metastatic uveal melanoma.

Authors

Francesca Rifaldi, Filippo De Braud, Michele Del Vecchio, Lorenza Di Guardo

Published in

Frontiers in immunology. Volume 17. Pages 1934256. Epub Oct 12, 2026.

Abstract

Tebentafusp improves survival in HLA-A*02:01-positive metastatic uveal melanoma, yet the human evidence linking early systemic immune activation to remodeling of metastatic tumors is dispersed across overlapping translational reports.
We performed a PRISMA-style, search-informed narrative review and descriptive evidence mapping of human reports evaluating baseline or on-treatment immune measurements in tebentafusp-treated uveal melanoma. PubMed/MEDLINE, Embase, and CENTRAL were searched for reports published from January 2015 to 9 December 2025, with an updated search on 9 June 2026. Reports were linked to their underlying trial or cohort before synthesis.
Overall, 286 records were screened, 21 full-text reports or complete abstracts were assessed, and 10 reports were retained. These represented three principal evidence units rather than 10 independent studies: NCT02570308, NCT03070392, and an independent serial skin-biopsy cohort. Blood-based analyses consistently showed early cytokine induction and transient lymphocyte changes after tebentafusp dosing. Paired metastatic-tissue analyses reported increased CD3 and CD8 cell density and interferon-response programs by day 16, but these observations derived predominantly from overlapping analyses of NCT02570308. Baseline and on-treatment immune features were associated with survival in exploratory analyses. Skin biopsies provided independent evidence of on-target cutaneous pharmacodynamics but only indirect evidence regarding metastatic tumor remodeling.
Tebentafusp is associated with consistently observed early systemic immune activation across overlapping analyses, but treatment-associated metastatic tumor immune remodeling remains incompletely validated. The available evidence supports temporal coherence rather than a proven causal systemic-to-tumor pathway. Future studies should use prospective paired blood and liver sampling, harmonized time points, prespecified immune endpoints, and mediation analyses linking immune changes to clinical outcomes.

PMID:
42935816
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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