A series of immune responses leading to the induction of T cell IL-12/IL-18 responsiveness in patients with relatively large tumor burdens

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2003, Vol.52 (1), p.33-40
• Main Authors: UNO, Kazuko, MITSUISHI, Yoko, TANIGAWA, Mari, OKUNO, Kiyotaka, HIRAI, Norihiko, MIZUTANI, Youichi, SAOTOME, Hideo, FUJIWARA, Hiromi, KISHIDA, Tsunataro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD56 Antigen - analysis; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Female; Gene Expression Regulation, Neoplastic - drug effects; Host-tumor relations. Immunology. Biological markers; Humans; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukin-12 - biosynthesis; Interleukin-12 - blood; Interleukin-12 - genetics; Interleukin-12 - pharmacology; Interleukin-18 - pharmacology; Karnofsky Performance Status; Lymphocyte Activation - drug effects; Male; Medical sciences; Middle Aged; Neoplasm Metastasis; Neoplasms - blood; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - surgery; Postoperative Period; Receptors, Antigen, T-Cell - immunology; Recombinant Proteins - pharmacology; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-002-0329-8

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.