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Chemotherapy-induced changes of perforin expression in cytotoxic T lymphocytes and natural killer cells of colon carcinoma patients

Potent cytolytic machinery responsible for the protection against the neoplastic and altered-self cells is mainly related to the presence of cytoplasmatic granules containing molecule perforin and associated granzymes, which mediate target cell DNA degradation. AIM: To determine the effects of standard chemotherapy with 5-fluorouracil and leucovorin in colon carcinoma patients on expression of perforin in peripheral blood mononuclear cells (PBMNC) and their subsets. METHODS: The blood samples were taken from 15 colon cancer patients, classified as Dukes^B or Dukes^C, before the operation and during the chemotherapy. The control group comprised of normal age-mated laboratory donors. Simultaneous detection of cell surface membrane antigens and intracellular content of perforin was made by flow-cytometry. RESULTS: The data showed that the percentage of total perforin positive cells among the PBMNC in colon cancer patient during the chemotherapy was 30% higher than in the control group. Double staining of surface markers and perforin content revealed that augmented particularly CD8+ T lymphocytes (19, 5 % versus 10% in control group ; p<0, 01). The calculation of the frequency of perforin expressing cells in the various lymphocytes phenotype also showed that after chemotherapy the percentage of perforin positive cells among the CD3+ cells arose to 55, 70% (versus 18% in the healthy population) and among the CD4+ cells to 6, 20% (versus 3, 5%). The frequency of perforin positive cells among the populations of CD16+ and CD56+ cells was, however, found to be declined, from 68% to 51, 49%, and from with 92% to 63, 1%, respectively. CONCLUSION: The data emphasize the marked changes induced by chemotherapy in cytotoxic T lymphocytes and cells with NK phenotype, pointing to the important role of cytolytic molecule perforin in immune reaction on aberrant cells.

chemotherapy; perforin; NK cells; cytotoxic lymphocytes; colon cancer

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