Hierarchical Immunosuppression of Regional Lymph Nodes in Patients with Head and Neck Squamous Cell Carcinoma

Abstract

Patients with head and neck squamous cell carcinomas (HNSCCs) manifest defects in cell-mediated immune function. Previous studies in this laboratory have demonstrated regional alterations in the immunocompetence of draining lymph nodes (LNs) in HNSCC patients. In this investigation, we studied functional activity of lymphocytes from lymph nodes in different locations in the radical neck dissections (RNDs) from patients undergoing operations for HNSCC. Lymphocytes from nodes close to the primary tumor (“near” lymph nodes or NLN) exhibited a significant decrease in interleukin-2 (IL-2)-activated cytotoxicity when compared to lymphocyes from distant nodes (“far” lymph nodes or FLN). In addition, co-culture experiments suggested the existence of a soluble regulatory factor, produced by lymph nodes, that inhibited the development of lymphokine-activated killer (LAK) cells in vitro. Further experiments with conditioned supernatants from the lymph node cells confirmed the presence of this soluble inhibitory factor. The inhibitory effect is significantly greater in NLNs than in FLNS. This hierarchical phenomenon suggests a regional network of immunosuppression in HNSCC patients. It is likely that tumor- and lymph node-induced suppression plays a role in limiting the efficacy of current immunotherapy protocols in human beings. A greater understanding of mechanisms of local inhibition of immune function will aid in improving adoptive immunotherapy for treatment of cancers in human beings.