Edward Baral

Blood lymphocytes in breast cancer patients following radiotherapy and surgery

Abstract Peripheral blood lymphocytes from 110 subjects with primary carcinoma of the breast were studied before and at various times after local radiotherapy and/or surgery. The results demonstrated that the recovery of the relative PPD (purified protein derivative) responses of the lymphocytes after radiotherapy progresses more rapidly than the repopulation of the total lymphocyte population.

Evidence for the appearance of non-specific suppressor cells in the blood after local radiation therapy.

Radiation therapy for carcinoma of the breast may induce lymphopenia and a reduction of the purified protein derivative (PPD) tuberculin reactivity of the lymphocytes in vitro as measured on a cell-for-cell basis. In the present investigation we have examined whether the reduced PPD-reactivity after irradiation can be explained by the appearance of non-specific suppressor cells. The results confirm that the reactivity of non-purified lymphoid cell preparations decreases significantly after radiotherapy. This reduction was not correlated to the extent of radiation induced lymphopenia. In contrast, lymphoid cell preparations depleted of adherent cells do not exhibit any significant decrease, indicating that monocytes-macrophages may become non-specifically immunosuppressive after local radiotherapy.

Reductions of responder and stimulator capacities of peripheral lymphoid cells in the mixed lymphocyte culture following external radiotherapy.

The peripheral lymphoid cells of patients with primary cancers of the breast, urinary bladder or prostate were examined, before and after radiotherapy, for capacity to respond and stimulate in the mixed lymphocyte culture using lymphoid cells from healthy donors as allogeneic cells. Radiotherapy reduced both the responder and stimulator capacities of the peripheral lymphoid cells to approximately the same extent in the same individual. These reductions were not correlated to the extent of radiation induced lymphopenia. The results suggest a general defect of the peripheral lymphoid cell population after radiotherapy.

Natural Killer Activity in Peripheral Lymphocyte Population Following Local Radiation Therapy

The natural killer (NK) activity of peripheral lymphocytes against 51Cr-labelled Chang or K562 cells was tested using a 4 h release assay before and after postoperative radiation therapy for mammary carcinoma. NK activity against K562 was significantly reduced at completion of therapy (a total target dose of 45.0 Gy) and restituted 3 to 4 months later. NK activity against Change cells exhibited a slight but non-significant decline at completion of therapy followed by an overshoot 3 to 4 months later. The frequency of Fc-IgG receptor bearing lymphocytes was decreased at completion of therapy and largely restored after 3 to 4 months.

Changes of the peripheral lymphocyte population following radiation therapy to extended and limited fields

Abstract The peripheral lymphoid cell populations were examined in 2 groups of breast cancer patients. One group had been treated by wedge excision of the tumor and received postoperatively 5000 rad in 5 weeks through tangential fields encompassing the breast only (limited field treatment). The other group consisted of patients who had been treated by modified radical mastectomy; postoperatively, they received 4500 rad in 5 weeks to the internal mammary, supraclavicular and axillary lymph node regions and the chest wall (extended field treatment). Patients receiving extended field treatment developed the most pronounced lymphopenia. In both groups of patients 2 subpopulations of non- T -lymphocytes, cells possessing receptors for C ′3 and cells binding mouse erythrocytes, were depleted to a higher extent than T-cells. The first mentioned populations, however, repopulated faster than the latter. The response of the cells in the mixed lymphocyte culture (MLC) was reduced to the same extent in both groups and correlative studies could not establish any relation between the extent of radiation induced lymphopenia and reduction of MLC responsiveness. Relative phytohemagglutin (PJA) responses, however, were reduced to a higher extent in patients receiving extended field treatment. The results support the concept that radiation induced impairment of antigen reactivity cannot entirely be explained by decreased lymphocyte counts but also by the triggering of immunosuppressive mechanisms such as activation of inhibitor cells.

Changes in mixed lymphocyte culture (mlc) functions of peripheral lymphoid cells after radiation therapy for breast carcinoma

Abstract Peripheral lymphoid cells of patients with breast cancer were tested for their capacity to function as andstimulators in mixed lymphocyte culture (MLC before and after local radir local radiation therapy. Both of these MLC functions were decreased after therapy and returned to pretreatment levels within 3–4 months. Both the responder and stimulator capacities of the cell preparations obtained at completion of radiation therapy were increased by depleting phagocytic cells. These results are consistent with the view that immunosuppression observed shortly after radiation therapy results partly from the appearance of non-specific suppressor cells with monocyte characteristics.

Long-term effects on the immune system following local radiation therapy for breast cancer. 4. Proliferative responses and induction of suppressor activity of the blood lymphocyte population

The long-term effect of local irradiation for breast cancer on the blood lymphocyte population was examined in 149 women who had been disease-free for 5-6 and 10-11 years. The patients were included in a clinical trial aiming at determining the value of pre- and post-operative irradiation (45 Gy) compared to surgery only. It was observed that the relative mitogen responses of lymphocytes to phytohaemagglutinin (PHA) and Concanavalin (Con A) and in a mixed lymphocyte culture (MLC) were significantly lower in irradiated compared to unirradiated patients at least a decade after treatment. The prolonged reductions of mitogen responses after irradiation could partly be due to an increased proportion of lymphocytes which may express suppressor function since the Con A-inducible suppressor activity of lymphocytes was significantly higher in irradiated compared to unirradiated patients.

Prognostic Relevance of Immunologic Variables in Breast Carcinoma

A series of 203 consecutive patients with operable carcinoma of the breast was analysed with regard to correlations between a set of immunologic and clinical variables existing at the time of the diagnosis. No major correlations were revealed between immunologic variables on the one hand and clinical features or the course of the disease on the other. The well-known prognostic relevance of tumour size, involvement of the axilla and the histological grade of malignancy was evident.

Incidence of Infectious Symptoms after Radiation Therapy for Breast Cancer: Long-term effects

The incidence of symptoms generally associated with infectious disease was assessed by a questionnaire sent out to 519 disease-free breast cancer patients 7 to 12 years after primary treatment. All patients were treated in the context of a randomized trial where pre- and postoperative radiation (45 Gy) was evaluated versus surgery only. The results indicate a significantly higher morbidity among patients treated with preoperative irradiation compared with those irradiated postoperative (p less than 0.05). This increased morbidity mainly seemed to be caused by symptoms usually associated with respiratory tract infection (p less than 0.05). Although statistically not significant the preoperatively irradiated patients also had a higher morbidity than those treated with surgery alone. There was no difference between postoperatively irradiated patients and patients treated with surgery only. A significantly higher integral dose (absorbed energy within the body) of the pre- compared with the postoperative group (p less than 0.025) is associated with the differences in morbidity between the two irradiated groups. An explanation for the increased morbidity seems to be that the volume of lung tissue, encompassed within the full-dose target volume, is the crucial factor. This volume was considerable in the preoperatively treated patients but kept at a minimum in the postoperative group.

Adjuvant Radiation Therapy Compared with Cyclic Chemotherapy in Patients with Mammary Carcinoma: I. Changes of blood lymphocyte subpopulations

Peripheral lymphocyte subpopulations were examined in 37 women with breast carcinoma who were postoperatively randomized to adjuvant local radiation therapy or cyclic treatment with 5-Fluorouracil, Methotrexate and Chlorambucil. Both T and non-T lymphocyte counts were reduced but the latter subpopulation was reduced to the highest relative extent in both groups of patients. Following radiation therapy the non-T cells repopulated more rapidly than the T cells, whereas the repopulation seemed to be the reverse in patients treated with chemotherapy.