Expression of signal transducing T-cell receptor ζ molecules after adoptive immunotherapy in patients with gastric and colon cancer

✍ Scribed by Koji Kono; Fumiko Ichihara; Hidehiko Iizuka; Takayoshi Sekikawa; Yoshiro Matsumoto

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 97 KB
• Volume: 78
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19981029)78:3<301::aid-ijc7>3.0.co;2-z

✦ Synopsis

We and others have shown decreased expression of T-cell receptor-CD3-associated signal transducing molecules (TCR) in tumor infiltrating and peripheral T cells of patients with advanced cancer. In the present study, we performed adoptive immunotherapy (AIT) with tumor-associated lymphocytes (TAL) in patients with gastric (n ‫؍‬ 11) and colon (n ‫؍‬ 3) cancer with stage IV and investigated whether the alteration of signal transducing molecules was observed with AIT, compared to an untreated control group (n ‫؍‬ 13). Autologous TALs isolated from malignant ascites or pleural effusion were cultured with stimulation of autologous tumor in the presence of interleukin-2 (IL-2) and were transferred to the patients. TCR expression in peripheral T cells was measured by flow cytometric analysis of permeabilized cells with anti-monoclonal antibody (MAb) (TIA-2) before and after AIT. We confirmed the down-regulation of TCR expression in peripheral blood lymphocytes (PBL) of patients with gastric and colon cancer with stage IV compared to healthy donors (n ‫؍‬ 15). AIT induced up-regulation of TCR expression in 2 of 14 treated patients, caused no significant change of TCR expression in 7 patients and induced further down-regulation in 5 patients. The patients who achieved clinical responses (n ‫؍‬ 3) with AIT showed no significant change of TCR expression. On the other hand, in the control group without adoptive transfer, further down-regulation of TCR expression was observed during the corresponding periods, paralleling disease progression. Taken together, TCR expression in the patients was further down-regulated, corresponding to disease progression in individual cancer patients. In some patients, AIT could induce increased or stable TCR expression. The quantitative analysis of TCR expression might provide vital information that can be used to optimize therapy by preserving immune functions within cancer patients.