Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2012-06, Vol.61 (6), p.771-782
• Main Authors: Berinstein, Neil L., Wolf, Gregory T., Naylor, Paul H., Baltzer, Lorraine, Egan, James E., Brandwein, Harvey J., Whiteside, Theresa L., Goldstein, Lynn C., El-Naggar, Adel, Badoual, Cecile, Fridman, Wolf-Herve, White, J. Michael, Hadden, John W.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antigens; Antineoplastic agents; Biological and medical sciences; Biopsy; Cancer; Cancer Research; CD3 antigen; CD4 antigen; CD8 antigen; Clinical trials; Cytokines; Cytokines - administration & dosage; Cytokines - immunology; Female; Fibrosis; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Human papillomavirus; Humans; Immunohistochemistry; Immunology; Immunotherapy; Laboratories; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Macrophages; Male; Medical sciences; Medicine; Medicine & Public Health; Metastases; Middle Aged; Necrosis; Oncology; Original Article; Otorhinolaryngology (head neck, general aspects and miscellaneous); Otorhinolaryngology. Stomatology; Pharmacology. Drug treatments; Regression Analysis; Squamous cells; Stains; Stroma; Surgery; Survival Analysis; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-011-1134-z

Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.