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March 1995

Production by Human Squamous Cell Carcinoma of a Factor Inducing Activation and Proliferation of Immune Cells

Author Affiliations

From the Departments of Otolaryngology (Drs Hirabayashi, Johnson, and Whiteside), Pathology (Drs Yasumura, Lin, Herberman, and Whiteside) and Medicine (Dr Herberman), University of Pittsburgh (Pa) School of Medicine; Pittsburgh Cancer Institute (Drs Hirabayashi, Yasumura, Lin, Amoscato, Johnson, Herberman, and Whiteside); and Pittsburgh Eye and Ear Institute (Drs Hirabayashi and Johnson).

Arch Otolaryngol Head Neck Surg. 1995;121(3):285-292. doi:10.1001/archotol.1995.01890030025005

Objective:  To examine supernatants (SNs) of human squamous cell carcinoma of the head and neck cell lines for soluble tumor-derived factors capable of inducing activation and proliferation of human immune cells.

Design:  The SN of squamous cell carcinoma of the head and neck cell line PCI-50 was cultured in serum-free medium and tested for the ability to induce expression of activation antigens, proliferation, cytotoxicity against tumor cell targets and cytokine production by purified human natural killer (NK) and CD4+ T cells.

Results:  Supernatant of PCI-50 promoted expression of the following activation markers on NK and T cells: CD25 (interleukin-2R-α), HLA-DR (major histocompatibility complex class II), CD54 (ICAM-1), CD71 (transferrin receptor), and CD69 (activation-inducing molecule). In addition, SN induced and significantly sustained (P<.01) proliferation of human unseparated peripheral blood lymphocytes and NK or T cells in culture. Purified human NK or T cells cultured in the presence of the SN and IL-2 (120 IU/mL) had significantly higher antitumor cytotoxicity than that mediated by NK or T cells cultured in AIM-V medium and IL-2. The SN induced cytokine (interferon γ, tumor necrosis factor a, interleukin-6) production in purified NK or T cells. When the SN was fractionated by molecular weight-based filtration into fractions greater and less than 30 kd, the growth- and cytotoxicitypromoting activities were consistently detectable in the greater than 30-kd fraction.

Conclusions:  Culture SN of squamous cell carcinoma of the head and neck cell lines contain a soluble factor(s) capable of activating NK and CD4+ T cells and of promoting growth and antitumor cytotoxicity of these lymphocyte subsets in vitro.(Arch Otolaryngol Head Neck Surg. 1995;121:285-292)