37P - Identification of immune profile in advanced cutaneous squamous cell carcinoma predicting immunotherapy response

Background

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer, characterized by malignant proliferation of epidermal keratinocytes. If treated at an early stage with surgical excision, the 5-year cure rate is over 90%. However, in a minority of cases, they are diagnosed at locally advanced(lacSCC) or metastatic(mcSCC) stages, not amenable to surgery, radiotherapy, or a combination of both. Cemiplimab, a monoclonal antibody anti-PD-1, is the first drug approved for the treatment of mcSCC and lacSCC. Here we show how the expression levels of cytokines and chemokines in patients undergoing treatment vary compared to baseline, and how these variations correlate with treatment response.

Methods

Cytokine profiling is the objective of this study, in the research of potential parameters that specifically respond to Cemiplimab treatment. PBMCs from the blood of lacSCC patients or healthy donors were collected. The expression levels of genes encoding for immune checkpoint (PD-L1, CTLA4) and of several proinflammatory cytokines, such as CXCL8 IL-6, IL-1β, IL12, TNFα, IFNγ and anti-inflammatory ones (IL4, IL-10) were analyzed by RT-qPCR. We performed a baseline sample at the start of treatment on both populations, then we conducted sample every 2 cycles on patients in treatment.

Results

Increase of CXCL8 expression was found in patients in treatment, and specifically, the increase in CXCL8 was linked with the timing of clinical response. Patients in clinical response showed a subsequent reduction in CXCL8 that persists and correlates with the maintenance of clinical response.

Conclusions

CXCL8 appears to be a predictive marker of response in the early stages of treatment in patients who respond to Cemiplimab.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Troiani: Financial Interests, Personal, Principal Investigator: Regeneron. C.M. Della Corte: Financial Interests, Personal, Invited Speaker: Regeneron. All other authors have declared no conflicts of interest.