Tumor-Infiltrating Lymphocytes in Breast Cancer. Association with Clinical and Pathological Parameters.

In patients with primary resectable breast cancer, a positive correlation between the age and the count of CD16+ lymphocytes and a negative correlation of this parameter with the number of regulatory CD4+CD25+CD127- cells and proliferative activity of Ki-67 tumor cells were revealed. Higher level of Ki-67 was associated with reduced number of effector lymphocytes (CD8+ and CD16+) and elevated content of regulatory CD8+CD11b-CD28- T cells. The absence of expression of estrogen receptors was associated with reduced cytotoxic potential of CD8+ T cell in comparison with ER+ breast cancer. The percentage of CD8+ lymphocytes (CD3+CD8+ and CD8+CD11b+CD28+) among lymphocytes infiltrating the tumor was higher in PR+ breast cancer than in PR- tumors. With increasing the tumor load, the number of lymphocytes expressing CD16 marker and their cytotoxic potential decreased.

[Lymphocyte receptors that regulate the immune-response--the key to the management of antitumor immunity].

Tumor uses various mechanisms to "escape" from immune surveillance including the important role of dysregulation of interaction of signals from corresponding co-stimulatory and co-inhibitory receptors (so-called "control points immunity"-- immune "checkpoints") modulating T-cell activation process. A creation of targeted drugs impacting on immune "checkpoints"" is a new promising trend in modern oncoimmunology. This review is devoted to a brief characterization of some receptors of immune competent cells (such as activation and inhibitor), which play a crucial role in the interaction of the immune system and tumors as well as targeted drugs acting on them for therapeutic purpose.

[Phenotype of immunocompetent cells and its role in antitumour immune response].

The paper contains an overview of the role of certain minor subpopulations of lymphocytes in tumour growth and of the main results obtained in the studies of the phenotype of immunocompetent cells from cancer patients. Special attention is given to selected indicators of immunity as predictors of the disease and efficacy of immunotherapy.

Variations in the number of regulatory T cells (CD4+CD25+) in patients with breast cancer during herceptin therapy.

We studied the effect of Herceptin therapy on the population composition of lymphocytes and percentage of CD4+CD25+ cells (regulatory T cells) in breast cancer patients. Herceptin treatment decreased the number of "professional" T suppressors (CD4+CD25+ cells and regulatory T cells) in the peripheral blood.

[Accumulation of vitamin E in dimethylnitrosamine-induced kidney tumors in rats with various levels of alpha-tocopherol supplementation]. / Nakoplenie vitamina E v opukholiakh pochek krys, indutsirovannykh dimetilnitrozoaminom, pri razlichnom obespechenii zhivotnykh alpha-tokoferolom.

The effect of a long-lasting loading with alpha-tocopherol on the development of dimethylnitrosamine-induced kidney tumors was investigated in 55 non-bred white male rats. The carcinogen was repeatedly introduced into the stomach by means of a gastric tube. Starting 24 days after the last administration of the carcinogen the alpha-tocopherol loading began and lasted up to the end of the experiment. 21 rats were loaded with vitamin E introduced into the stomach, 5 times a week at a dose of 70 mg/kg body weight. 17 rats received sunflower seed oil--the vitamin E solvent; other 17 rats received only standard ration. The control group (20 rats) were not treated with the carcinogen. One part of these rats received alpha-tocopherol by the above schedule while another part--sunflower oil alone. It was shown that the alpha-tocopherol loading had no effect on the incidence of renal tumors. Nevertheless it enhanced to some extent the rate of their development as well as the incidence of blastomes in other organs. Based on histological examination, tumors developed in kidneys were of epithelial and mesenchymal origins with the mesenchymal tumors occurring more frequently (63-69% of the total). Vitamin E content in tumor tissue of rats, loaded or not loaded with alpha-tocopherol, was much higher than that in intact kidneys of corresponding control animals, suggesting a high tumor tropism of this vitamin. Total lipid concentration of tumor tissue was 1.5 times lower than that of intact kidneys. Histological nature of tumors had no visible effect on their vitamin E and total lipid content.

[Reverse correlation between natural resistance of mice to transplanted leukemia EL-4 and rectal temperature]. / Obratnaia korreliatsiia mezhdu estestvennoi rezistentnost'iu myshei k perevivaemomu leikozu EL-4 i rektal'noi temperaturoi.

Mice F1 (CBA x C57Bl) life span after transplantation of standard number of leukemia EL-4 cells at different clock hours was evaluated. At the same time, as injection was done, rectal temperature of mouse was measured. Both parameters showed circadian trend. Mice life span was in negative correlation with rectal temperature. So it is possible to consider temperature rhythm as marker rhythm of natural antitumor resistance.

[Potentiation by blastolysin of the effect of cyclophosphamide in preventing recurrence in mouse T-cell leukemia]. / Potentsirovanie blastolizinom protivoretsidivnogo éffekta tsiklofosfamida pri T-kletochnom leikoze myshei.

Injection of cyclophosphamide in a dose of 100 mg/kg two or four times at 18- or 7-day intervals, respectively, prolonged the remission in EL-4-leukemia-bearing C57Bl/6j mice induced by cytosar under deoxycytidine protection. Injection of blastolysin in a dose of 25 mg/kg once a week at the same period had no effect. However, blastolysin potentiated the antirelapse effect of cyclophosphamide. It is suggested that the potentiation of the cyclophosphamide effect with blastolysin is mediated by activation of antitumor immunological reactivity.

[Characteristics of hematopoietic system reactions of newborn and adult mice to the growth of syngeneic hepatoma H-2-73]. / Osobennosti reaktsii krovetvornoi sistemy novorozhdennykh i vzroslykh myshei na rost singennoi gepatomy H-2-73.

The growth of syngeneic hepatoma H-2-73 in adult (CBA x C57BL/6j) F1 mice leads to the development of leukemoid response that is manifested by leukocytosis, splenomegaly and a considerable increase in the content of lymphoid cells in the spleen. Meanwhile the newborn recipients of the tumor do not develop leukemoid response but manifest physiological changes in the hemopoietic tissue normally occurring within the first weeks after birth. The sensitized cells of the spleen of the adult tumor-bearing mice enhance tumor growth in the newborn recipients and inhibit it in the adult mice. Spleen cells of normal adult donors do not affect tumor growth in the newborn recipients. The data obtained suggest that the opposite effect of the transferred sensitized spleen cells from the adult animals on tumor growth in the newborn and adult mice is related to the age-associated features of the immune system of recipient mice.

[Effect of sublethal pretransplantation irradiation on the growth of syngeneic tumors in newborn mice]. / Vliianie subletal'nogo pretransplantatsionnogo oblucheniia na rost singennykh opukholei u novorozhdennykh myshei.

Subcutaneous transplants of hepatoma and ovarian carcinoma strains grew slower in a group of newborn mice preirradiated with a sublethal dose of 750 R as compared with groups of intact newborn and adult animals. Sublethal preirradiation of adult mice in a dose of 600 R produced no steady effect on the subsequent growth of the tumors.