Tumor metastases and cell‐mediated immunity in a model system in DBA/2 mice. V. Transfer of protective immunity with H‐2 identical immune T cells from B10.D2 mice

Abstract

Evidence is presented for the existence of immune T lymphocytes which have protective activity in vivo against the lethal effects of a metastasizing tumor. ESb, the metastasizing tumor cell line of our model system, which i s highly malignant in syngeneic DBA/2 mice, can be rejected when transplanted into B1O.DZ mice. Since B1O.DZ and DBA/2 mice are identical a t the H-2 complex, cells could be transferred from the tumor-resistant into the susceptible strain t o determine whether they could confer protective immunity i n a syngeneic environment containing disseminated ESb tumor cells. Protective immunity against ESb could be transferred into DBA/2 with spleen cells but not with ascites fluid from B1O.DZ mice preimmunized against the ESb tumor cells. B1O.DZ spleen cells taken between 6 and 22 days after tumor transplantation had protective immunity, while cells taken from animals 3 days after tumor transplantation, or from normal animals, had no significant protective effect. The cells in B1O.DZ immune spleens with protective activity were sensitive t o treatment with anti-theta serum and complement and did not adhere t o nylon-wool columns. Such nylon-wool column-passed cells which were enriched for T lymphocytes had a higher protective activity then the unfractionated cells. DBA/Z mice which received viable ESb tumor cells subcutaneously on day 0 could be protected by intravenous inoculation of B1O.DZ immune spleen cells only when these were given after the tumor cells (day +l, +3, +5, +7), not when given before (day -3 o r -1). The mechanisms of protective immunity against tumor metastasis and the significance of our findings for completely syngeneic tumor systems will be discussed.When tumor cells metastasize, they spread primarily from their site of origin via the lymphatics or the blood circulatory system. One can anticipate that in these vessels only those tumor cells which are resistant to the mechanical shear forces as well as to attacks by the host's immune system will survive. Furthermore, for the establishment of metastases in internal organs, such tumor cells must be able to adhere to and penetrate the endothelial membranes of the vessels and find a proper microenvironment for successful growth. Since both blood and lymph harbor a number of elements of the immune system, both humoral and cellular, many kinds of interactions with the disseminated tumor cells probably occur. Some components might facilitate, others might inhibit, the process of tumor cell spreading.To investigate such interactions between metastasizing tumor cells and elements of the immune system in more detail, we have recently established a model system in mice. This consists of two related tumor lines, a metastasizing cell line (ESb) and a non-metastasizing one (Eb), both derived from a chemically induced lymphoma (L5178Y) of the DBA/2 mouse. With regard to local growth and pattern of invasion and metastasis the tumor cells of our system seem to resemble quite accurately extra-nodal lymphomas in humans (about 20 % of human lymphomas...

Antigenic variation in cancer metastasis: immune escape versus immune control

“…Protective immunity against ESb could be transferred into DBA/2 with spleen cells but not with ascites fluid from anti-ESb immune B10.D2 mice. B10.D2 spleen cells taken between six and 22 days after tumor transplantation had protective immunity, while cells taken from animals three days after tumor transplantation or from normal animals had no significant protective effect (111). In this experimental protocol protective immunity is not measured in a Winn assay.…”

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

“…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)(8)(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), or through the inoculation of viable parental Eb cells into a site refractory to the growth of these cells [intra-ear pinna (i.e.)].…”

Inhibition by Lymph Node Cells and Promotion by Fetal Hepatocytes of Murine Tumours without or with Chemotherapy

“…The timing of the cell injections was broadly in agreement with a schedule used successfully in experi ments in which immune T lymphocytes were trans ferred in a syngeneic environment from a tumourresistant strain into a strain susceptible to the chem ically induced ESb lymphoma in DBA/2 or B10.D2 mice [16]. The effective cell dose corresponds also to the one used in experiments in which newborn mice were protected against a plasmocytoma by injection of non-immune cells [8],…”