title: A series of immune responses leading to the induction of T cell IL-12/IL-18 responsiveness in patients with relatively large tumor burdens.
abstract: The induction of interleukin-12 (IL-12) responsiveness in T cells depends on T cell receptor (TCR) triggering, and is regarded as a parameter of recently TCR-sensitized T cells. Here, we investigated whether IL-12 responsiveness could be detected in freshly prepared T cells from tumor-bearing patients, and if so whether such patients exhibited additional immunological parameters related to IL-12 responsiveness. CD4(+) and CD8(+) T cell populations from an appreciable proportion of tumor-bearing patients exhibited high levels of IL-12 responsiveness as evaluated by IL-12-stimulated interferon-gamma (IFN-gamma) production. T cell populations with high IL-12 responsiveness were observed in the group of patients with moderate to large tumor mass or tumor metastases rather than in patients with small tumors. The frequency of such a T cell population was also lower in post-surgery tumor-free patients, showing the correlation between IL-12 responsiveness and the presence of a certain extent of tumor burden. More importantly, a higher incidence of IL-12 responsiveness was observed in tumor-bearing patients exhibiting detectable plasma IL-12 levels, and correlated with IL-18 responsiveness. T cell IL-12 and IL-18 responsiveness is induced by TCR triggering and subsequent IL-12 stimulation respectively. Furthermore, TCR-triggered T cells stimulate antigen-presenting cells (APC) to produce IL-12. Therefore, the present observations suggest that an immune response loop from TCR sensitization to the induction of IL-12/IL-18 responsiveness via IL-12 production operates in tumor-bearing patients, particularly in those with relatively large tumor burdens.
authors.affiliation: Louis Pasteur Center for Medical Research, 103-5, Tanaka Monzen-cho, Sakyo-ku, Kyoto, Kyoto 606-8225, Japan. KazukoUNO@lpc-dns.louis-pasteur.or.jp
authors.forename: Kazuko
authors.initials: K
authors.lastname: Uno
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mitsuishi
authors.forename: Mari
authors.initials: M
authors.lastname: Tanigawa
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.forename: Norihiko
authors.initials: N
authors.lastname: Hirai
authors.forename: Youichi
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Hideo
authors.initials: H
authors.lastname: Saotome
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Tsunataro
authors.initials: T
authors.lastname: Kishida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D020382:Interleukin-18 / Q000494:pharmacology*; D017567:Karnofsky Performance Status; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D011184:Postoperative Period; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D019002:CD56 Antigen; D020382:Interleukin-18; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma