Patients with SCCHN are consistently found to have disordered immune function at the time of presentation. Although they have normal B-cell function, immunoglobulin levels, and complement systems, SCCHN patients have immunological deficiencies of T-cell anergy and defective monocyte/macrophage function.1,2 Human SCCHN tissues commonly expressed PD-L1, which downregulates T-cell mediated immunity.3
The cumulative result of the various immune defects and immunosuppressive mechanisms in SCCHN is1,2,4:
Because tumors induce immune suppression through multiple mechanisms, immunotherapy should encompass multiple mechanisms to effectively counteract tumor-induced immune suppression. Based on the immune defects observed, strategies for active immunotherapy may include:
The checkpoint inhibitors pembrolizumab and nivolumab are indicated for second-line therapy in patients with recurrent or metastatic SCCHN, demonstrating the importance of immunotherapy in SCCHN.
IRX-2 is a proprietary therapeutic containing numerous active cytokine components, which restore and activate multiple immune cell types, including T cells, dendritic cells, and NK cells, that are able to recognize and destroy tumors.4-8 IRX-2 leads to an increase in tumor activation markers, including PD-L1,9 suggesting a complementary role with checkpoint inhibitors.