Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection.

Abstract

Live proliferation-competent and Irradiated proliferation-incompetent L5178 murine lymphoma cells (Eb cell line) were compared for their potency to induce systemic anti-tumor Immunity in syngeneic DBA/Z mice. The tumorigenic potential in vivo of live Eb cells was suppressed through local secretion of interleukin 4 (IIA) Failure to develop effective tumor-rejection immune responses has been suggested to be due to a deficiency of help generated within the immune system (1, 2). In accordance with this postulate, the potential immunotherapeutic effects of a number of lymphokines have been tested through immunization of syngeneic or immunodeficient animals with tumor cell lines that have been engineered to secrete particular lymphokines for help. Protocols using multiple vaccinations at optimal doses have been successful in identifying combinations oftumor systems and lymphokines where local lymphokine secretion is effective for systemic anti-tumor protection (3) or even in the therapy of established micrometastases (4). Other recent investigations (using singlevaccination protocols) have found that, with the exception of granulocyte/macrophage-colony-stimulating factor, local secretion of lymphokines achieve little if any improvement on the immunogenicity of the irradiated parental tumor cells (5,6).The present investigation addresses the influence of tumor cell viability (when used as vaccine) on the induction and maintenance oflong-lasting anti-tumor immunity. To this aim we have employed the well-characterized L5178 lymphoma line Eb, which expresses characteristic Kd-associated tumor antigens and elicits specific cytotoxic T-cell responses in immunized or tumor-bearing syngeneic hosts (7-9). Vaccination of syngeneic DBA/2 mice with live tumor cells was achieved either through local secretion of interleukin 4 (1L4), which is known to render tumor cells nontumorigenic (10,11) 7430The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Cognate interactions between memory T cells and tumor antigen‐presenting dendritic cells from bone marrow of breast cancer patients: Bidirectional cell stimulation, survival and antitumor activity in vivo

“…17 We could demonstrate that low numbers of proliferation-competent tumor cells coexisted in a tumor dormancy situation with CD8 immune memory T cells, which constantly kept the level of tumor cells around 100 per 1 million bone marrow cells. 18 Many primary operated breast cancer patients also contain in their BM low numbers of tumor cells.…”

Treatment with annexin V increases immunogenicity of apoptotic human T-cells in Balb/c mice

“…For instance, cellular tumour vaccines usually display a poor immunogenicity if the cancer cells are irradiated before injection. 35,36 Thereby, irradiation-induced apoptosis may result in a non-inflammatory engulfment by macrophages and, in addition, an anti-inflammatory effect of apoptotic cells on human monocytes/macrophages. 14,15 Based on our immunisation experiments with xenogeneic apoptotic cells we assume that treatment with AxV may also increase the immunogenicity of irradiated tumour vaccines.…”

Stabilization of β-catenin induces lesions reminiscent of prostatic intraepithelial neoplasia, but terminal squamous transdifferentiation of other secretory epithelia

“…Immunoperoxidase staining was according to instructions of the kit manufacturer (SS MultiLink Detection Kit, HRP/DAB-BioGenex, QD200-OX). b-galactosidase activity was revealed on 6 mm cryosections as described (Khazaie et al, 1994).…”