T-cell abnormalities after mediastinal irradiation for lung cancer. The in vitro influence of synthetic thymosin alpha-1.
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 degrees C (E4 degrees-RFC)/mm3, E-rosette-forming cells at 29 degrees C (E29 degrees-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 phytohemagglutinin under suboptimal conditions (P less than or equal to 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 degrees-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.
Schulof
R S
RS
Chorba
T L
TL
Cleary
P A
PA
Palaszynski
S R
SR
Alabaster
O
O
Goldstein
A L
AL
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008482:Mediastinum / Q000528:radiation effects*; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000528:radiation effects*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D013947:Thymosin; D000077596:Thymalfasin