Abstract Purpose:
The purpose of this work was to assess the capacity of tumor-infiltrating leukocytes (TIL) from human non-small-cell lung carcinoma (NSCLC) specimens to synthesize type-1 and type-2 cytokines. Methods: TIL were isolated from tumors following digestion with collagenase/DNase and further enriched by ficoll-hypaque gradient centrifugation. Membrane phenotypes and intracellular cytokine protein expression of TIL were assessed by flow cytometry. Results: The majority of TIL expressed the CD3 antigen with a CD4:CD8 ratio of approximately 2:1. Other leukocytes such as macrophages (CD14), B lymphocytes (CD20), and natural killer (NK) cells (CD56) were also found to infiltrate the tumors, but in significantly lower numbers. Owing to the limited recovery of non-CD3+ leukocytes, our analysis of cytokine biosynthesis has focused on T lymphocytes. In the absence of activation, a small percentage of CD3+ TIL synthesized cytokines ( <4%). Following activation with anti-CD3+interleukin-2 (IL-2), CD3+ TIL synthesized predominantly a type-1 cytokine profile; however, the type-2 cytokines, IL-6 and IL-10, were also detected in a small percentage of infiltrating cells. Following activation with phorbol 12-myristate 13-acetate + ionomycin, CD3+ TIL also expressed more type-1 than type-2 cytokines and in significantly greater numbers of cells. The CD3+CD8+ component of the TIL synthesized only type-1 cytokines, whereas the CD3+CD4+ component synthesized both type-1 and type-2 cytokines. Conclusion: These results show that the majority of the TIL isolated from NSCLC specimens are T lymphocytes with the capacity to synthesize type-1 cytokines.
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Received: 24 March 1999 / Accepted: 9 September 1999
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Ortegel, J., Staren, E., Faber, L. et al. Cytokine biosynthesis by tumor-infiltrating T lymphocytes from human non-small-cell lung carcinoma. Cancer Immunol Immunother 48, 627–634 (2000). https://doi.org/10.1007/s002620050011
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DOI: https://doi.org/10.1007/s002620050011