Lymph node histology in head and neck cancer: impact of immunotherapy with IRX-2 Abelardo Meneses a,1 , Emma Verastegui a , Jose L. Barrera a , Jaime de la Garza a , John W. Hadden b, * a The National Institute of Cancerology, Mexico City, Mexico b University of South Florida Medical College, Tampa FL, USA Received 1 October 2002; received in revised form 18 November 2002; accepted 18 November 2002 Abstract Objective: To determine if lymph nodes (LN) of patients receiving IRX-2 immunotherapy reflect changes in histology. Setting: National Cancer Institute, Mexico City, Mexico. Patients: Thirty patients with advanced squamous cell carcinoma of the head and neck (H&N SCC) and 10 non-cancer controls. Intervention: A 21-day cycle of preoperative immunotherapy, including a single intravenous infusion of low-dose cyclophosphamide (300 mg/M 2 ), 10 or 20 daily perilymphatic injections of a natural cytokine mixture (IRX-2) (approximately 200 U interleukin-2 equivalence by enzyme-linked immunosorbent assay), daily oral indomethacin, and daily oral zinc with multivitamins, followed by surgery (20 patients); surgery only (10 patients); LN biopsy controls (10). Outcome measures: Pretreatment biopsies were performed to confirm the diagnosis. Clinical responses were assessed at surgery, and the specimen and a sample of lymph node were analyzed with respect to changes in morphology and lymphoid and inflammatory infiltration (T and B lymphocytes, plasma cells, macrophages, granulocytes, and giant cells). The postsurgical characteristics were ascribed percentages based on a representative section and compared. Results: All 20 H&N SCC patients treated with IRX-2 showed the changes of immune regression of their tumors, previously characterized [Arch. Pathol. Lab. Med. 122 (1998) 447]. The 10 H&N SCC controls showed no such changes. Lymph node histology of the 10 H&N SCC controls showed, compared to non-cancer controls, reduced size, decreased T cell area and density and increased sinus histiocytosis. The lymph nodes of IRX-2-treated H&N SCC patients showed increased size (over both control groups), increased T cell area and density and decreased follicles and sinus histiocytosis. The T cell and/or B cell areas of LN of IRX-2-treated patients showed a high correlation with T and/or B cell infiltration into these tumors ( p < 0.001). Conclusion: The lymph nodes of patients with H&N SCC are distinguished by T cell depletion and sinus histiocytosis (SH). Immunotherapy reverses these changes and induces nodal expansion and lymphoid infiltration into the tumor that correlates with LN changes. The correlation of nodal expansion with tumor lymphoid infiltration and regression implies an effective immunization to host tumor antigens occurring at the level of the regional lymph node. The reversal of sinus histiocytosis, by IRX-2 treatment, in association with nodal expansion suggests 1567-5769/03/$ - see front matter D 2003 Published by Elsevier Science B.V. doi:10.1016/S1567-5769(03)00017-1 * Corresponding author. 428 Harbor Road, Cold Spring Harbor, NY 11724, USA. Tel.: +1-516-692-4551; fax: +1-516-692-6319. E-mail address: jwhadden@optonline.net (J.W. Hadden). 1 Request for reprints: Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando, Tlalpan, Mexico DF, Mexico. www.elsevier.com/locate/intimp International Immunopharmacology 3 (2003) 1083 – 1091