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Inhibition of lymphokine-activated killer cell generation by blocking factors in sera of patients with head and neck cancer

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Summary

Cytolytic activation of peripheral blood lymphocytes by recombinant interleukin-2 (rIL-2) in patients with squamous cell carcinoma (SCC) of the head and neck may be inhibited by serum blocking factors, and this could influence therapeutic efficacy. Peripheral blood lymphocytes from 21 patients with this disease and 17 controls were incubated with 10–1000 U rIL-2 for 6 days in supplemented complete medium (containing 10% fetal calf serum) or the same medium plus 10% autologous serum. After washing the effector cells, we determined their cytotoxicity against K562 and MDA1386, a lymphokine-activated-killer(LAK)-sensitive SCC cell line, using a51Cr-release assay. Patient sera inhibited LAK-generated lysis of both MDA 1386 and K562, while control sera from healthy persons inhibited LAK-generated lysis of MDA1386. The blocking activity of patient sera tended to be greater than that of control sera. The sera of patients with untreated or recurrent disease and those who were free of disease had equivalent inhibitory capacity. The serum blocking factor acted in a dose-dependent manner, and inhibition was overcome by increasing the dose of rIL-2. Levels of circulating immune complexes (measured by the Clq binding method) did not correlate significantly with inhibition. A clinical protocol of repeated plasma exchange in patients with advanced and recurrent squamous cell carcinoma of the head and neck allowed sequential study of one patients's serum before, during, and after treatments. Plasmapheresis removed serum inhibitory factors, albeit temporarily. The activity of serum blocking factors in patients with this disease can be modulated by increasing doses of rIL-2 and by plasma exchange. This modulation may be important to improving clinical response rates for patients undergoing immunotherapy.

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Authors and Affiliations

  1. Department of Surgery, Queen's University, Kingston, Ontario, Canada

    Samuel P. Bugis

  2. Department of General Surgery, The University of Texas M.D. Anderson Cancer Center, 77030, Houston, Texas, USA

    Eva Lotzová

  3. Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 69, 77030, Houston, TX, USA

    Howard E. Savage, Tamas Racz, Peter G. Sacks & Stimson P. Schantz

  4. Hematology, The University of Texas M.D. Anderson Cancer Center, 77030, Houston, Texas, USA

    Jeane P. Hester

Authors
  1. Samuel P. Bugis
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  2. Eva Lotzová
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  3. Howard E. Savage
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  4. Jeane P. Hester
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  5. Tamas Racz
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  6. Peter G. Sacks
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  7. Stimson P. Schantz
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Bugis, S.P., Lotzová, E., Savage, H.E. et al. Inhibition of lymphokine-activated killer cell generation by blocking factors in sera of patients with head and neck cancer. Cancer Immunol Immunother 31, 176–181 (1990). https://doi.org/10.1007/BF01744733

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  • DOI: https://doi.org/10.1007/BF01744733

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