Publication Description
The effects of mediastinal irradiation (RT) on the numbers and functions of purified peripheral blood T‐lymphocytes from patients with locally advanced non‐small cell lung cancer were evaluated. The patients were candidates for a randomized trial to evaluate the immunorestorative properties of synthetic thymosin alpha‐1. Twenty‐one patients studied before RT did not exhibit any significant difference in T‐cell numbers or function compared to age‐matched healthy subjects. However, 41 patients studied within 1 week after completing RT exhibited significant depressions of E‐rosette‐forming cells at 4°C (E4°‐RFC)/mm3, E‐rosette‐forming cells at 29°C (E29°‐RFC)/mm3, OKT3/mm3, OKT4/mm3, and OKT8/mm3 (P = 0.0001); total T‐cell percentages (%OKT3, P = 0.01); and T‐cell proliferative responses in mixed lymphocyte cultures (MLR) (P = 0.01) and to the mitogen phytohe‐magglutinin under suboptimal conditions (P ≤ 0.03). Nine patients studied before and after RT showed a significant increase in OKT4/OKT8 (P = 0.01) following RT. A short‐term in vitro incubation with thymosin alpha‐1 could enhance MLR of T‐cells in 12 of 27 patients with post‐RT abnormalities. In 13 patients who were treated with placebo, the RT‐induced depression of T‐cell numbers and function persisted for at least 3 to 4 months. In addition, in 12 patients progressive decreases developed in %E4°‐RFC, %OKT3, %OKT4, and OKT4/OKT8. which always preceded clinical relapse. This study indicates that mediastinal RT results in prolonged depletion of circulating T‐cells, alterations of T‐cell subset proportions, and intrinsic T‐cell functional deficiencies. This patient population provides a uniformly immunosuppressed group of subjects with which to evaluate the immunorestorative effects of thymosin alpha‐1 or other biologic response modifiers.