title: Differential expression of granulysin and perforin by NK cells in cancer patients and correlation of impaired granulysin expression with progression of cancer.
abstract: Granulysin has been identified as an effector molecule co-localized with perforin in the cytotoxic granules of cytotoxic T lymphocytes and natural killer (NK) cells, and has been reported to kill intracellular pathogens in infected cells in the presence of perforin and to induce a cytotoxic effect against tumor cells. The aim of the present study was to elucidate whether intracellular expression of granulysin and perforin by NK cells might be associated with progression of cancer. Flow cytometric analysis demonstrated high levels of perforin and granulysin expression by CD3(-) CD16(+) cells in healthy controls. In contrast, cancer patients exhibited significantly decreased levels of granulysin expression ( P<0.005), despite having equally high levels of perforin expression in comparison with healthy controls. The tumor-free patients expressed granulysin at levels similar to healthy controls, while the progressive tumor-bearing patients expressed remarkably lower levels of granulysin compared to healthy controls ( P<0.0001). Similarly, patients with an advanced performance status had significantly fewer granulysin-positive NK cells than healthy controls. Meanwhile, a considerable number of the tumor-bearing patients showed a decrease in the number of circulating NK cells, and a correlation between impaired granulysin expression and reduced circulating NK cells was observed. These findings suggest that the tumor-bearing patients with impaired granulysin expression were in an immunosuppressive state. In conclusion, impaired expression of granulysin by NK cells correlates with progression of cancer, and determination of granulysin expression might prove informative for assessing the immunological condition of cancer patients.
authors.affiliation: Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan. Kishia@lpc-dns.louis-pasteur.or.jp
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kishi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takamori
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ogawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takano
authors.forename: Shuji
authors.initials: S
authors.lastname: Tomita
authors.forename: Mari
authors.initials: M
authors.lastname: Tanigawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Niman
authors.forename: Tsunataro
authors.initials: T
authors.lastname: Kishida
authors.forename: Setsuya
authors.initials: S
authors.lastname: Fujita
mesh_terms: D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis* / Q000276:immunology; D014408:Biomarkers, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011379:Prognosis
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D014408:Biomarkers, Tumor; C075005:GNLY protein, human; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin