Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans

J. T. Rubin, L. J. Elwood, S. A. Rosenberg, M. T. Lotze

Research output: Contribution to journalArticle

Abstract

We have evaluated immunohistochemical characteristics of tumors and the infiltrating cells in patients treated with various immunotherapy regimens. Forty-eight patients with advanced malignancies were treated with high dose i.v. recombinant interleukin-2 alone or in combination with cyclophosphamide, recombinant tumor necrosis factor, recombinant interferon-α, antimelanoma antibody 9.2.27, adoptively transferred tumor infiltrating lymphocytes, or lymphokine-activated killer cells. Thirty-four patients with metastatic melanoma and two patients with breast carcinoma underwent excision of one or more s.c. metastases either before, during, or after treatment. Twelve patients with metastatic renal cell carcinoma underwent pretreatment nephrectomy and these tumors were also studied. Tumor cells were evaluated for class I (HLA-A,B,C) and II (HLA-DR) antigen expression and the mononuclear infiltrate was characterized using an avidin-biotin immunoperoxidase technique. All melanomas were class I antigen positive. Fifty-three % of biopsied metastatic melanoma lesions, 58% of primary renal cell carcinomas, and neither of the two breast carcinomas expressed class II antigen prior to therapy. The pretreatment expression of class II antigens by a tumor was not predictive of a clinical response to recombinant interleukin 2-based therapy. After treatment, however, seven of seven biopsied regressing individual metastases intensely expressed DR antigen on over fifty percent of the cells while only three of ten nonresponding lesions did so. Regressing lesions were permeated with macrophages and both CD4 and CD8 T-cell subsets. There were no CD1 or NKH-1 positive infiltrating cells detected in any lesion. The response to recombinant interleukin 2-based immunotherapy is associated with T-cell as well as macrophage infiltration. DR antigen expression by tumor cells and T-cell infiltrate appear in individual lesions to be associated with this response.

Original languageEnglish (US)
Pages (from-to)7086-7092
Number of pages7
JournalCancer Research
Volume49
Issue number24 I
StatePublished - 1989
Externally publishedYes

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Immunotherapy
Interleukin-2
Melanoma
Histocompatibility Antigens Class II
Neoplasms
Renal Cell Carcinoma
Macrophages
Breast Neoplasms
Neoplasm Metastasis
T-Lymphocytes
Tumor-Infiltrating Lymphocytes
Lymphokine-Activated Killer Cells
Histocompatibility Antigens Class I
HLA-A Antigens
HLA-B Antigens
Avidin
T-Lymphocyte Subsets
HLA-DR Antigens
Neoplasm Antigens
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Rubin, J. T., Elwood, L. J., Rosenberg, S. A., & Lotze, M. T. (1989). Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. Cancer Research, 49(24 I), 7086-7092.

Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. / Rubin, J. T.; Elwood, L. J.; Rosenberg, S. A.; Lotze, M. T.

In: Cancer Research, Vol. 49, No. 24 I, 1989, p. 7086-7092.

Research output: Contribution to journalArticle

Rubin, JT, Elwood, LJ, Rosenberg, SA & Lotze, MT 1989, 'Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans', Cancer Research, vol. 49, no. 24 I, pp. 7086-7092.
Rubin, J. T. ; Elwood, L. J. ; Rosenberg, S. A. ; Lotze, M. T. / Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. In: Cancer Research. 1989 ; Vol. 49, No. 24 I. pp. 7086-7092.
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