title: Colorectal carcinoma-derived fibroblasts modulate natural killer cell phenotype and antitumor cytotoxicity.
abstract: Substantial evidence indicates that cancer-associated fibroblasts (CAFs) are critical components in the process of cancer progression. However, the role of CAFs in the immunopathogenesis of human cancer remains elusive. In this study, we demonstrate that purified colorectal carcinoma-derived fibroblasts exhibit activated phenotypes characterized by substantial α-smooth muscle actin expression. These CAFs sharply suppress natural killer (NK) cell functions in co-culture experiments. In contrast, normal skin fibroblasts had only a minimal effect on NK cell phenotype and function. Moreover, we demonstrated that prostaglandin E2 (PGE2) was released by fibroblasts in co-culture experiments. Thus, the functional modulation of NK cells by CAFs may represent a novel mechanism linking the pro-inflammatory response to immune tolerance within the tumor milieu.
authors.affiliation: Department of Hepatic Surgery, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Tuanjie
authors.initials: T
authors.lastname: Li
authors.forename: Shuhong
authors.initials: S
authors.lastname: Yi
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Changchang
authors.initials: C
authors.lastname: Jia
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Hua
authors.forename: Yan
authors.initials: Y
authors.lastname: Tai
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Guihua
authors.initials: G
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D018920:Coculture Techniques; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes; D015232:Dinoprostone