The role of regulatory T lymphocytes in immune control of MC-2 fibrosarcoma.

The role of T regulatory lymphocytes (Treg) particularly in cancer is well known. The goal of the present study was to determine the contribution of these lymphocytes in the regulation of anti-tumor immunity of CBA/HZgr mice against MC-2 fibrosarcoma (4th generation of methylcholanthrene induced tumor). The levels of T lymphocytes (CD4+, CD8+ and CD4+CD25+) were determined 8 and 20 days after tumor transplantation. Further, the role of CD4+CD25+ (Tregs) in tumor-host interaction was evaluated in vitro and in vivo by using specific monoclonal antibodies. We found that splenocytes of both control and Treg depleted tumor bearing mice strongly but differently inhibited growth of tumor cells in vitro. While splenocytes of untreated mice exhibited significant decrease of this activity (from 74.4% to 62.6% and 32.95%), the splenocytes of Treg depleted mice showed increase of this activity (from 79.5% to 84.3% and 86.2%) from day 6 to day 13 and day 21 after tumor grafting, respectively. Further, upon i.v. injecting specific monoclonal anti-Treg antibody tumor immediately prior to tumor cell intracutaneous transplantation, the tumor was rejected after initial growth. In treated mice, the incidence of Treg cells was very low initially, reaching normal values two weeks later. These animals were shown to be resistant to tumor transplantation four months later.

Transplanted tumor growth and the incidence of T-lymphocyte populations in the spleen of newcastle virus-treated mice.

C3Hf/HZgr mice were transplanted with SCCVII carcinoma cells and treated with Newcastle disease virus (NDV). The treatment slows down the growth of transplanted tumor. Furthermore, by using specific monoclonal antibodies, the frequencies of CD4+, CD8+, and CD4+CD25+ T lymphocytes were determined in the spleen of tumorous mice at particular times following tumor transplantation and/or NDV application. The incidence of lymphocytes CD4+ and CD8+ decreased and of CD4+CD25+ increased in the spleen of mice during the time following tumor transplantation. However, the frequency of regulatory CD4+CD25+ T lymphocytes in the spleen is very low, while CD4+ and CD8+ increased to normal level following intraperitoneal (i.p.) NDV injection in tumor-bearing mice. Thus, besides directly destroying transplanted tumor, NDV seems to be involved against growing tumor by reducing the frequency of regulatory T lymphocytes maintaining the frequency of CD4+ and CD8+ T lymphocytes within the control values pointing to its role in immunomodulation.

The characterization of blood flow changes in mouse tumor during Photofrin-based photodynamic therapy by using the color Doppler ultrasonography.

Changes in blood flow velocity through the tumors can induce damage of tumor microcirculation and thus may contribute to the final destruction of tumor masses after photodynamic therapy (PDT). The aim of this study was to evaluate the blood flow changes in a SCCVII mouse carcinoma during Photofrin-based photodynamic therapy by analyzing several quantitative spectral Doppler parameters [maximum systolic flow velocity (Vmax), end diastolic velocity (Vmin), resistance index (RI) and pulsatile index (PI)] by using the color Doppler ultrasonography. Blood flow velocities were recorded immediately prior to tumor illumination (0 h) and then 2 and 24 h after the illumination. Statistically significant increase in diastolic blood velocity (Vmin) with a corresponding decline in RI and PI was recorded in tumors of the Photofrin-injected mice prior to tumor illumination. However, 2 h after the illumination a pronounced decrease in both Vmin and Vmax was obtained. There were no changes of these parameters in controls at different times during determination. The observed changes of spectral Doppler parameters in tumors from the PDT group point to the transition of tumor blood vessels from the relaxation state recorded before tumor illumination into a state of increased contraction after the activation of Photofrin by light. Pronounced changes in tumor blood vessel tone might be an additional stress for such vessels leading to their ultimate destruction.

Combined action of virus injection and local tumor irradiation on tumor growth in mice.

The dynamics of SCCVII transplantable tumor growth in C3H/H mice was determined after local tumor irradiation and/or virus (NDV LaSota) i.p. injection. The virus applied alone significantly suppressed tumor growth, particularly until the 19th day after tumor transplantation. Local irradiation with 30 Gy resulted in tumor disappearance followed with its regrowth about 15 days later. However, if the virus was injected after the irradiation, there was no tumor growth until the end of the 31 day observation period. It should be noted that virus application prior to local irradiation did not have any additional influence on tumor growth. Thus, the pronounced efficacy of virus applied after tumor irradiation deserves attention. It is possible that the virus injected after irradiation induced a chain of cytokine production joining the action of tumor destruction induced by irradiation. This should be further studied in clarifying the approaches to combined tumor therapy with possible cell-free vaccine production.