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

Abstract

We and others have shown decreased expression of T-cell receptor-CD3- associated signal transducing ζ molecules (TCRζ) 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 ζ expression in peripheral T cells was measured by flow cytometric analysis of permeabilized cells with anti-ζ 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 ζ expression in 2 of 14 treated patients, caused no significant change of TCR ζ 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 ζ expression. On the other hand, in the control group without adoptive transfer, further down-regulation of TCR ζ expression was observed during the corresponding periods, paralleling disease progression. Taken together, TCR ζ 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 ζ expression. The quantitative analysis of TCR ζ expression might provide vital information that can be used to optimize therapy by preserving immune functions within cancer patients.