Cell-mediated immunity in breast cancer patients

In clinical practice, reports have been made on immunosuppression after surgical excision of primary tumor or at relapse. However, the relationship between undefined or overt metastases and the host immune system has not been sufficiently examined over a prolonged period. These aspects were investigated in 160 breast cancer patients followed up post-operatively with serial controls over a long period. One hundred and thirty-four cases (91 node negative, (N-), 43 node positive (N+)) were disease-free and 26 relapsed. In all patients, serum T cell populations, serum B lymphocytes and skin reaction of delayed hypersensitivity (SRDH) were serially determined for 39 +/- 12 months (m +/- SD). The reference values for these parameters were assessed as follows: T populations were evaluated in 24 healthy donors and SRDH in 95 healthy females. In non-relapsed patients, constant CD8+ T cell decrease and T4/T8 ratio increase were observed; the T4/T8 ratio was significantly higher (ranging from P < 0.05 - P < 0.001) than in the control group. The mean values of NK cells and B lymphocytes, the former parameter being highly significant (P < 0.001), were higher than in controls. In the 26 metastatic patients, the T4/T8 ratio from 20 months before to 30 months after the first sign of relapse decreased from 3.2 to about 1 (r = -0.256, P < 0.05) and from 30 to 92 months after relapse progressively increased to 2. Similarly, in the former subinterval a progressive decrease in the number of positive antigens and score was found (from 2.4 to 0 and from 10 to zero respectively). A significant inverse correlation between these two parameters and observation time occurred (P < 0.01 and P < 0.001 respectively). From 30 to 86 months after relapse, a progressive increase in the number of positive antigens and scores up to 2 and 12 were observed. A significant direct correlation (P < 0.05) was noted. In conclusion, these data indicate significant changes in T populations during the disease-free interval in breast cancer patients. The decrease in circulating CD8+ T cells is compatible with the hypothesis of CD8+ T cell localization at the site of the micrometastases. The increase in circulating B lymphocytes and NK cells suggests activation of aspecific humoral immunity and NK function. In addition, they show that progressive deficiency in cell-mediated immunity appears many months before and that recovery continues for a long time after overt metastatic disease.