title: The presence of interleukin-2 receptor alpha in the serum of colorectal cancer patients is unlikely to result only from T cell up-regulation.
abstract: It is unclear whether the presence of interleukin-2 soluble receptor alpha (IL-2 sRalpha) in the serum of colorectal cancer patients is solely due to T cell activation. In this study, we therefore investigated whether T cell activation, indicated by the up-regulation of the CD25 and HLA-DR markers, or cell-mediated immunity (CMI) were associated with increased serum levels of IL-2 sRalpha in patients with advanced colorectal carcinoma. The levels of serum IL-2 sRalpha and the proportion of T cells expressing HLA-DR (DR(+) T cells) were measured as markers for chronic activation. CMI was assessed by delayed-type hypersensitivity reaction (DTH) to intradermal injections of recall antigens. Eighty-seven colorectal liver metastases (CLM) patients and 23 'cancer-free' control subjects were studied. DR(+) T cells were found to be more prevalent ( P<0.0001) in CLM patients (median: 21.1%) than in controls (median: 3.4%), but DR(+) T cell up-regulation was not correlated with serum IL-2 sRalpha levels. CMI positivity was significantly reduced ( P=0.002) in CLM patients compared with controls, and this reduction was significantly associated ( P=0.05) with an increase in the number of DR(+) T cells. Although survival was significantly shorter ( P=0.0003) in patients with increased serum IL-2 sRalpha levels than in subjects with normal levels, no association was found between survival and DR(+) T cell up-regulation. These findings were consistent with the hypothesis of an additional source of serum IL-2 sRalpha other than T cell up-regulation in CLM patients -- either from other immune cells, or from tumour products.
authors.affiliation: Department of Surgery, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK.
authors.forename: Andy
authors.initials: A
authors.lastname: Huang
authors.forename: Helen
authors.initials: H
authors.lastname: Quinn
authors.forename: Clare
authors.initials: C
authors.lastname: Glover
authors.forename: Don C
authors.initials: DC
authors.lastname: Henderson
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Allen-Mersh
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood* / Q000276:immunology / Q000401:mortality; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007111:Immunity, Cellular; D007121:Immunocompetence; D007249:Inflammation / Q000097:blood / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D007428:Intradermal Tests; D015993:Life Tables; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens; D015850:Interleukin-6; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I