This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Herpen, C. M.L. Articles by De Mulder, P. H.M. Search for Related Content PubMed PubMed Citation Articles by van Herpen, C. M.L. Articles by De Mulder, P. H.M.

Intratumoral Recombinant Human Interleukin-12 Administration in Head and Neck Squamous Cell Carcinoma Patients Modifies Locoregional Lymph Node Architecture and Induces Natural Killer Cell Infiltration in the Primary Tumor

Departments of ¹ Medical Oncology, ² Pathology, and ³ Tumor Immunology, UMC Nijmegen, Nijmegen, the Netherlands

Requests for reprints: Carla van Herpen, Department of Medical Oncology, UMC Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Phone: 0031-24-3610353; Fax: 31-24-3540788; E-mail: C.vanherpen{at}onco.umcn.nl.

The objective of this study was to evaluate the histologic and immunohistopathologic effects of intratumorally given recombinant human interleukin-12 on the immune cells in the primary tumors and regional lymph nodes. Ten previously untreated patients with head and neck squamous cell carcinoma (HNSCC) were injected in the primary tumor twice to thrice, once weekly, at two dose levels of 100 or 300 ng/kg, before surgery. These patients were compared with 20 non-IL-12-treated control HNSCC patients. In the primary tumor, the number of CD56⁺ natural killer (NK) cells was increased in IL-12-treated patients compared with control patients. In some IL-12-treated patients, an impressive peritumoral invasion of CD20⁺ B cells was noticed. No differences were seen in the CD8⁺ or CD4⁺ T lymphocytes. Interestingly, major differences were apparent in the architecture of the enlarged lymph nodes of IL-12-treated patients; in particular, the distribution of B cells differed and fewer primary and secondary follicles with smaller germinal centers were observed. In addition, a decrease of dendritic cell lysosyme-associated membrane glycoprotein–positive cells in the paracortex was noted, resulting in a reduction of paracortical hyperplasia. In the lymph nodes, especially the CD56⁺ NK cells but also the CD8⁺ and CD4⁺ T lymphocytes, produced a high amount of IFN-. Patients, irrespectively of IL-12 treatment, with a high number of CD56⁺ cells in the primary tumor had a better overall survival than those with a low number. In conclusion, after i.t. IL-12 treatment in HNSCC patients, the largest effect was seen on the NK cells, with a higher number in the primary tumor and a high IFN- mRNA expression in the lymph nodes. Significant effects were noted on B cells, with altered lymph node architecture in every IL-12-treated patient and excessive peritumoral infiltration in some patients.

Key Words: Phase II study • immunohistochemical • B cell • DC-LAMP • IFN-

This article has been cited by other articles:

				M. Matsui, T. Kishida, H. Nakano, K. Yoshimoto, M. Shin-Ya, T. Shimada, S. Nakai, J. Imanishi, T. Yoshimoto, Y. Hisa, et al. Interleukin-27 Activates Natural Killer Cells and Suppresses NK-Resistant Head and Neck Squamous Cell Carcinoma through Inducing Antibody-Dependent Cellular Cytotoxicity Cancer Res., March 15, 2009; 69(6): 2523 - 2530. [Abstract] [Full Text] [PDF]

				M. Del Vecchio, E. Bajetta, S. Canova, M. T. Lotze, A. Wesa, G. Parmiani, and A. Anichini Interleukin-12: Biological Properties and Clinical Application Clin. Cancer Res., August 15, 2007; 13(16): 4677 - 4685. [Abstract] [Full Text] [PDF]

				J. S. Schleypen, N. Baur, R. Kammerer, P. J. Nelson, K. Rohrmann, E. F. Grone, M. Hohenfellner, A. Haferkamp, H. Pohla, D. J. Schendel, et al. Cytotoxic Markers and Frequency Predict Functional Capacity of Natural Killer Cells Infiltrating Renal Cell Carcinoma Clin. Cancer Res., February 1, 2006; 12(3): 718 - 725. [Abstract] [Full Text] [PDF]