Immune System Modulation and Outcome in High-risk cSCC Treated With Surgery and Radiotherapy

Inclusion Criteria: * Age ≥ 18 years. * Signed written informed consent. * Histologically confirmed diagnosis of cSCC. * cSCC categorized as high risk according to ASTRO Guidelines: * close or positive margins that cannot be corrected with further surgery (secondary to morbidity or adverse cosmetic outcome). * gross perineural spread, as identified by radiological or pathological assessment. * disease recurrence after a prior margin-negative resection. * pathological stage T3 and T4. * desmoplastic or infiltrative tumors in the setting of chronic immunosuppression at pathological exam, cSCC involving regional lymphnodes, with the exception of a single, small (\<3 cm) cervical lymph node harboring carcinoma, without extracapsular extension. * cSCC addressed to adjuvant radiotherapy as per clinical practice (a complete post-operative treatment should be administered with 50-54 or 60-66 Gy depending on the margin status). * Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Exclusion Criteria: * cSCC not eligible for surgery. * cSCC not eligible for adjuvant radiotherapy for any condition depending on disease characteristics or patient characteristics, co-morbidities or refusal. * Any concurrent investigational product, biologic, or hormonal therapy for cancer treatment. * Concurrent treatment with chemotherapy for the purpose of cSCC cure. * History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial. * Any major surgery, different from that planned for the protocol, in the 15 days before the protocol starting. * Any radiotherapy treatment in the 28 days before the protocol starting * Pregnant or breastfeeding.