34P - Linking early immunity changes to clinical outcomes in cutaneous squamous cell carcinoma following anti-programmed death cell-1 (PD-1) treatment

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.