Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck?

Abstract

Head and neck squamous cell carcinomas (SCCHN) are not rare malignancies and account for 7% of all solid tumors. Prognosis of SCCHN patients strongly depends on tumor extension, site of onset, and genetics. Advanced disease (recurrent/metastatic) is associated with poor prognosis, with a median overall survival of 13 months. In these patients, immunotherapy may represent an interesting option of treatment, given the good results reached by check-point inhibitors in clinical practice. Nevertheless, only a minor number of patients with advanced disease respond to immunotherapy, and, disease progressions/hyper-progressions are common. The latter could be a very difficult issue, especially in patients having a wide and highly symptomatic head/neck mass. Given the potentiality to boost the immune response of some local modalities, such as electrochemotherapy, a possible future approach may take into account the combination of electrochemotherapy and immunotherapy to treat patients affected by SCCHN, suffering from symptomatic lesions that need rapid debulking.

Assessment of Ablation Therapy in Pancreatic Cancer: The Radiologist’s Challenge

“…Several therapies both thermal and non-thermal have the ability to stimulate anti-tumor immunity. The immunemodulatory response evidence is currently the strongest related to radiotherapy, although data is accumulating for high-intensity focused ultrasound, radiofrequency ablation, reversible and irreversible electroporation (33)(34)(35).…”

Electrochemotherapy in Mucosal Cancer of the Head and Neck: A Systematic Review

“…In the era of innovative immunomodulatory drugs, a new paradigm has emerged to upgrade the local effect of ECT into a systemic one. The massive release of tumor antigens and the secretion of damage-associated molecular patterns (e.g., adenosine triphosphate, heat-shock proteins, and calreticulin) and cytokines (e.g., interferon-gamma, interleukin-2, and tumor necrosis factor-alpha) from electroporated tumor cells lead to the recruitment and activation of dendritic- and antigen-presenting cells, resulting in the induction of immunogenic cell death [ 54 ]. The combination of ECT and immunotherapy was found to be a promising treatment strategy in retrospective reviews in melanoma patients and is currently being tested in several prospective clinical trials [ 55 , 56 ].…”

Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: A Big and Intriguing Challenge Which May Be Resolved by Integrated Treatments Combining Locoregional and Systemic Therapies

“…Electrochemotherapy (ECT) is a methodology able to couple the “electroporation” of the cell membranes with the concomitant administration of antineoplastic drugs. Electroporation consists of the application of short-intensity pulsed electric fields to tumor cells, following which, the plasma membrane permeability to different hydrophilic drugs transiently increases, thus facilitating cellular uptake of cytotoxic agents [ 55 , 56 , 57 , 58 ]. ECT acts through three main mechanisms, namely, the so called “vascular lock”, which consists of a vascular spasm able to interrupt the tumor bleeding and to a prolong contact time between the antineoplastic drug and the tumor tissues; the second mechanism is the direct action of the drug with the cancer cells DNA, which leads to DNA damage and quick apoptosis; finally, the most interesting one regards the induction of the “immunogenic cell death” (ICD), which is characterized by the tissue expression of different immunogenic antigens and a strong recruitment of DC and APC.…”