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Histologic and immunohistochemical characterization of tumor and inflammatory infiltrates in oral squamous cell carcinomas treated with local multikine immunotherapy: the macrophage at the front line

  • Head and Neck Oncology
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European Archives of Oto-Rhino-Laryngology and Head & Neck Aims and scope Submit manuscript

Abstract

Squamous cell carcinomas of the head and neck (SCCHN) are excellent candidates for local immunotherapy owing to their accessibility and their infiltration by mononuclear cells that are susceptible to immunomodulation. A response rate of 25–60% has been reported for treatment with natural IL-2 or a mixture of natural lymphokines. In the present study, biopsies and posttreatment excision specimens from nine patients with operable SCCHN treated systemically with a variety of immunomodulators and locally with natural lymphokines (multikine, CelSci) were analyzed in an attempt to correlate clinical response to histopathological and immunohistochemical changes. Formalin-fixed, paraffin-embedded tissues were stained with antibodies against lymphocytes (CD45, CD3, CD4, CD8, CD20), macrophages (CD68) including dendritic cells (S-100), markers for lymphocyte activation (CD30, HLA-DR), natural killer cells (CD56 and CD57), beta-2-microglobulin and keratin. One patient showed a complete response to treatment and two a partial response. Tumor size was significantly smaller after therapy. Clinical and pathological regression were more prominent in the smaller tumors. Numerous macrophages, both mononucleated and multinucleated, were present along the tumor-stroma interface in the posttreatment specimens of seven patients, most prominently in the three patients with tumor regression. The increase in the number of CD68+ and S-100+ macrophages after treatment was statistically significant. Lymphocytic infiltrates, which showed some increase following treatment, were composed of a mixture of T and B lymphocytes, the former mostly in contact with the tumor and the latter placed more peripherally. CD8+ lymphocytes extended into the tumors, whereas CD4+ lymphocytes showed minimal extension. Intensity of beta-2-microglobulin staining in tumors was significantly higher following therapy and associated with a better outcome. The marked increase in macrophages following treatment may indicate that the macrophage plays a major role in tumor recognition, destruction and clearance. An increase in the number of macrophages in a posttreatment specimen may indicate immunoresponsiveness.

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Acknowledgements

The authors thank Gloria Ginzach and Charlotte Sachs of the Editorial Board, Rabin Medical Center, Beilinson Campus, for their assistance.

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Authors and Affiliations

  1. Pathology Institute, Beilinson Campus, Rabin Medical Center, 49100, Petah Tiqva, Israel

    Meora Feinmesser, Elimelech Okon & Ella Kaganovsky

  2. Department of Otolaryngology, Beilinson Campus, Rabin Medical Center, 49100, Petah Tiqva, Israel

    Elena Aminov, Ben Nageris & Raphael Feinmesser

  3. Felsenstein Medical Research Center, Beilinson Campus, Rabin Medical Center, 49100, Petah Tiqva , Israel

    Britta Hardy & Raphael Feinmesser

  4. Department of Epidemiology, Beilinson Campus, Rabin Medical Center, 49100, Petah Tiqva , Israel

    Jaqueline Sulkes

  5. Department of Pathology, Golda Campus, Rabin Medical Center, Petah Tiqva, Israel

    Ariel Schwartz

  6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Meora Feinmesser, Elimelech Okon, Ariel Schwartz, Ella Kaganovsky, Britta Hardy, Elena Aminov, Ben Nageris, Jaqueline Sulkes & Raphael Feinmesser

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  1. Meora Feinmesser
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Correspondence to Meora Feinmesser.

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This study is a CISEPO project and was supported in part by the Saul A. Silverman Family Foundation.

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Feinmesser, M., Okon, E., Schwartz, A. et al. Histologic and immunohistochemical characterization of tumor and inflammatory infiltrates in oral squamous cell carcinomas treated with local multikine immunotherapy: the macrophage at the front line. Eur Arch Otorhinolaryngol 261, 359–368 (2004). https://doi.org/10.1007/s00405-003-0615-x

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  • DOI: https://doi.org/10.1007/s00405-003-0615-x

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