Blood lymphocytes in breast cancer patients following radiotherapy and surgery.
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Biomedical subjects
Publications and source records attributed to B Petrini.
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Immunologic effects of unemployment were prospectively studied in women over a period of 8 months. Subjects were classified into three groups depending on their employment history, and were studied concomitantly. Group A consisted of unemployed women who were recipients of traditional support from the Swedish welfare state. Group B was composed of unemployed women who were given the opportunity to participate in a psychosocial program, in addition to receiving the traditional unemployment benefits received by group A. Group C, the control, consisted of securely employed women. Phytohemagglutinin (PHA) reactivity of lymphocytes decreased significantly in both groups of unemployed women after 9 months of unemployment. The psychosocial program did not counteract this decrease. Reactivity to purified protein derivative (PPD) of tuberculin also decreased significantly in the unemployed subjects. No changes were observed in the securely employed women. There were no significant differences among the groups in T cell subpopulations, B cells, and serum cortisol. The data suggest that some aspects of the immune system may be altered at a specific time period following the loss of work. Further studies are needed to see if this effect is only temporary or more long lasting.
Several investigators have shown a comparatively high prevalence of Candida albicans serotype B among HIV-infected individuals. We serotyped oral C. albicans strains from 50 HIV-infected homosexual men, 39 HIV-seronegative homosexual men and 40 clinical oral isolates of a control group. The prevalence of serotype B was significantly higher in homosexual men, regardless of HIV serostatus, than in the control subjects. We suggest that the reported high prevalence of serotype B among AIDS patients in Europe and the USA simply reflects the high proportion of homosexual men among HIV-infected patients. In 22 subjects, oral C. albicans isolates were obtained at two or more time points, up to 8 years apart. No change in serotype was observed over time. The serotype prevalences in HIV-infected patients with oral thrush or AIDS-defining illness were similar to the group of homosexual men as a whole, indicating that there is no serotype-related variation in pathogenicity.
The influence of postoperative cyclic chemotherapy for breast carcinoma on the blood lymphocyte population was examined in 21 recurrence-free women 4 to 6 years after completion of therapy. Chemotherapy consisted of combinations of chlorambucil, methotrexate and 5-fluorouracil or cyclophosphamide, methotrexate and 5-fluorouracil. It was observed that the lymphocyte numbers and mitogenic responses to PHA and in an MLC, known to be depressed during and shortly after treatment, had recovered to the levels of healthy age-matched women. NK activity, which is increased during the period of chemotherapy, still remained elevated.
Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease.
Mononuclear cells from blood of 19 breast cancer patients were cultured in vitro before and following postoperative radiation treatment. Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1) were determined in supernatants from stimulated and unstimulated cultures with or without addition of indomethacin. The release of all three cytokines was uninhibited in tumour patients. Spontaneous IL-1 secretion was increased in patients compared to controls. Indomethacin enhanced IFN-gamma release and spontaneous and induced TNF-alpha secretion in all groups but stimulated IL-1 only in irradiated patients. In patients with a low tumour burden, ability to produce cytokines seems to be unchanged although increased spontaneous IL-1 secretion indicates macrophage activation. Cyclooxygenase inhibition in conjunction with irradiation might be tried as a therapeutic modality in patients with cancer.
Changes of relative CD2 receptor on lymphocytes were examined in 11 women following radiation treatment for breast cancer by electron microscopy using antibody-coated gold particles. Proportions of blood lymphocytes with a high density of CD2 receptors were reduced, whereas those with no or a low density of such receptors were increased after radiation treatment.
The objective of this investigation was to examine further the influence of postoperative adjuvant treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) on the immune system in breast cancer patients and to explore whether such changes are related to prognosis. The 12 CMF courses which were given for a period of 1 year resulted in a progressive lymphopenia. The relative spontaneous secretions of IgA and IgG in vitro increased 4- and 2-fold respectively after the first 3 courses, whereas IgM secretion was unaffected. IgA and IgG secretions in PWM stimulated cultures were not changed, whereas there was a sharp decrease of IgM. The CMF-induced changes of Ig-secretions were similar in patients who developed recurrent disease during a 4-6 year follow-up (n = 11) and those who remained clinically disease-free (n = 14). The results are discussed in relation to the immunopotentiation which may occur following treatment with relatively low doses of chemotherapeutic agents.
Long-term effects of local radiotherapy (45 Gy) on the spontaneous and PHA-mediated cytotoxicity of the peripheral blood lymphocyte population was studied in disease-free breast cancer patients 5-6 and 10-11 years after treatment. The patients were all part of a randomized trial in which pre- or post-operative radiotherapy was evaluated against surgery only. PHA-mediated cytotoxicity for 51Cr-labelled chicken erythrocytes seemed to be somewhat increased in patients who were irradiated 5-6 years earlier (p less than 0.025). This increase was not detectable after a disease-free period of 10-11 years. No significant differences between the various treatment groups were observed for spontaneous cytotoxicity against Chang and K 562 cells. The proportion of Leu 7+ lymphocytes was significantly increased in patients who received radiation therapy 5-6 years earlier (p = 0.029) and there was a significant correlation between PHA-mediated cytotoxicity and proportion of Leu7+ cells.
The size of various subset of blood lymphocytes and stimulations with PHA and allogeneic cells (MLC) were examined in 45 women with breast cancer receiving postoperative adjuvant cyclic chemotherapy with chlorambucil, methotrexate, and 5-fluorouracil (LMF). The patients who remained disease-free (n = 19) and those who relapsed (n = 26) during a 4.5 to 6-year follow-up period had similar initial values; and similar kinetics of the examined immunological parameters during and following completion of treatment.
The capacity of PWM (poke-weed mitogen) to stimulate Ig-secretion by blood lymphocytes was examined before and at various times after local radiation therapy (46.0 Gy) for breast cancer. It was observed that the secretion of IgM, IgA and IgG were significantly reduced at completion of radiation therapy. Secretion of IgM was reduced to the highest relative extent (approximately 10% of the pretreatment value). Thereafter there was a recovery of the Ig-secreting capacity which, however, remained below the pretreatment level, 12-18 months after completion of radiation therapy. The capacity of PWM-stimulated blood lymphocytes to secrete specific antibodies against morbilli and herpes simplex virus was also significantly impaired after radiation therapy. The reduction of Ig-synthesis in vitro was not correlated with the increase in the ratio between numbers of monocytes and lymphocytes in peripheral blood after radiation therapy. Possible explanations for these results are discussed.
Reduction of nitroblue tetrazolium by blood monocytes was significantly increased following post-operative radiation therapy for breast cancer. Attachment and ingestion of yeast particles by monocytes was not affected. Exposure of purified monocytes in vitro to 13 Gy did not significantly affect NBT reduction of yeast particle attachment, whereas ingestion of yeast particles was slightly increased.