Abstract 34P
Background
The anti-Program Death 1 (PD1) Cemiplimab is the first-choice treatment in patients with advanced cutaneous squamous cell carcinoma (cSCC), when curative options are unavailable. However, reliable biomarkers for patient selection are still lacking.
Methods
In this translational study, clinical annotations, tissue and liquid biopsies were acquired to investigate the association between early and sustained objective responses with transcriptional profiles, immune cell dynamics in tumor tissue and peripheral blood, as well as circulating cytokine levels. We transcriptionally investigated early changes in immune-related gene sets associated with response to cemiplimab treatment.
Results
We observed that treatment induced increase of B cells and CD8+T cells in responders, while their abundance decreased in non-responder patients. Moreover, IL1β and IL8 exhibited early downregulation in samples acquired from responder patients. Next, we assessed whether changes in the local tumor microenvironment were mirrored in peripheral blood. Similar to tissue findings, no changes were observed in the whole Treg population, albeit PD1+ Tregs that were downregulated in responder patients (vs T0), whereas showed a rebound enrichment in non-responders after three cycles of cemiplimab. Finally, we determined that unlike IL1β, IL8 mirrored the tissue results, with early (T1) and then sustained (T3) downregulation of its levels in responder patients, while increased in non-responders.
Conclusions
Taken together, these findings shed light on the significance of early transcriptomic alterations and immune cell population modifications in predicting response to cemiplimab therapy. Additionally, our data suggest that IL8 levels in peripheral blood offer promising avenues for personalized treatment selection and response assessment in cSCC patients receiving cemiplimab, while PD1+ Tregs can be followed longitudinally to monitor response to therapy.
Legal entity responsible for the study
Luigi Formisano.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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