Abstract 1143P
Background
Cutaneous squamous cell carcinoma (cSCC) – the second most common skin tumor - accounts for 20% of all deaths from skin cancer. Although the vast majority of patients can be managed with surgical excision, a small percentage of them have locally advanced or metastatic tumors for which programmed cell death 1 (PD-1) checkpoint inhibition was approved and demonstrated substantial antitumor activity. The absence of reliable markers of response and the lacking of a description of immune modulation upon treatment, highlight a clinical need to be addressed.
Methods
We collected tumor and liquid biopsies of 12 patients underwent to cemiplimab before and after 3-weeks of treatment. We profiled RNA of pre- and post-cemiplimab tumor biopsies using the PanCancer Immunoprofile Panel (Nanostring). We determined cytokines released in blood by multiplex ELISA, and lymphocytes abundance by flow cytometry.
Results
The analysis of transcriptional reprogramming in tumor biopsies showed that PD1 blockade induced the expression of PD1-regulated genes after treatment. Interestingly, cemiplimab treatment boosted immune cell activation only in responders patients (i.e. B- and T-cells), according to the host antitumor response expected upon PD-1 targeting. Focusing on peripheral markers, total regulatory T cells (Tregs) early increased in non-responders patients, but dissecting specific antigens of Treg populations, we identified the specific T-cell costimulator (ICOS) subpopulation with a different trend in responders and non-responders. ICOS-positive cells, indeed, increased their abundance in the peripheral blood only of responder patients, in line with recent data showing ICOS cells as positive markers of ICI efficacy in lung cancer. Finally, TNF-α sera levels decreased after treatment only in responder patients, in line with its role as a determinant of resistance to PD1 targeting.
Conclusions
Our results provided new key elements to monitor response to therapy, determining putative markers to early define responsiveness to ICI in cSCC patients and suggest how to improve their clinical management.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Servetto: Financial Interests, Personal, Other: Eli Lilly, MSD, Janssen; Financial Interests, Institutional, Funding: AIRC. R. Bianco: Financial Interests, Personal, Advisory Board: BMS, MSD, Pfizer, AstraZeneca, Eli Lilly, Novartis. All other authors have declared no conflicts of interest.
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