| First Author | Ehrke MJ | Year | 1998 |
| Journal | Int J Cancer | Volume | 76 |
| Issue | 4 | Pages | 579-86 |
| PubMed ID | 9590137 | Mgi Jnum | J:47474 |
| Mgi Id | MGI:1203477 | Doi | 10.1002/(sici)1097-0215(19980518)76:4<579::aid-ijc22>3.0.co;2-1 |
| Citation | Ehrke MJ, et al. (1998) Thymic anti-tumor effectors in mice cured of lymphoma by cyclophosphamide plus TNF-alpha therapy: phenotypic and functional characterization up to 20 months after initial tumor inoculation. Int J Cancer 76(4):579-86 |
| abstractText | As reported previously, cyclophosphamide plus tumor necrosis factor-alpha treatment of C57BL/6 mice bearing advanced EL4 lymphoma induced approx. 60% long-term (i.e., >60 days) survivors. These mice developed protective immunity, as evidenced by 1) rejection (100% survival) of EL4 tumor re-implanted on day 60 (day 0 = initial tumor implantation); and 2) development of significant levels of specific EL4 tumor cell killing activity by both splenocytes and thymocytes. Using this model, age-related changes in functionally and phenotypically definable thymocyte subsets were assessed. In thymocytes from 90 to 308 day survivors, specific immune memory was long term; both CD4+ and CD8+ cells were required for the ex vivo stimulation of lytic activity, but the specific anti-EL4 cytotoxic effector was CD4-CD8+. On day 520, the surviving mice were randomized into 2 groups. One group received a second re-challenge with EL4 tumor cells and all survived. The other group was sacrificed on day 520. Their thymocytes, exposed to X- irradiated EL4, developed anti-EL4 lytic activity and, in comparison with thymocytes of young and age-matched control mice, were markedly enriched in CD4-CD8+CD44+ cells. On day 625, thymocytes from the survivors of the day 520 re-challenge were evaluated and were found to have developed specific anti-EL4 lytic activity. Phenotypically, they had returned toward the pattern seen in age-matched control mice although CD4-CD8+CD44+ cells remained increased. These mice were > or = 2 years old, the median life span of C57BL/6 mice. Thus, mice cured of tumor by an immuno-modulating regimen rejected re-implanted primary tumor and maintained specific thymic anti-tumor immune memory for life. |
