Immune surveillance and natural resistance: an evaluation

BALB/c mice were treated s.c. with 3-methylcholanthrene (MCA), and tumor incidence and growth were followed for 9 months. Immunological status of mice was altered by various treatments. Thymectomized, lethally irradiated, bone marrow reconstituted mice served as T-cell deficient recipients. In order to suppress natural killer (NK)-cell/macrophage functions some mice were injected with silica particles; to enhance these functions some mice were given Corynebacterium parvum (CP). Silica and CP were given simultaneously with MCA to test their influence on the presumed function of surveillance of tumor incidence, and also 2 months after MCA to test their influence on the growth of greater numbers of transformed host cells. Almost all mice developed tumors at the inoculation site and at the end of the observation period there was no difference in tumor incidence among 9 experimental groups. However, in T-cell deficient mice we observed shorter tumor duration and earlier death than in normal mice. Silica particles appeared to enhance tumor growth but the differences compared to normal controls were not significant. A single injection of CP simultaneously with MCA caused earlier tumor appearance but also slowed its growth. In contrast, CP given 2 months after MCA significantly delayed the appearance of the tumors. In regard to the tumor growth immunosuppression had stronger effects in males than in females; the opposite was true for immunostimulation treatments. We concluded that immunological status does not influence long-term tumor incidence, but that both T-cell and NK-cell/macrophage compartments strongly influence the parameters of growth of chemically induced tumors, i.e., the immune and natural resistance mechanisms do not influence the frequency of de novo arising tumors but both can slow down tumor growth.

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Incidence and growth of methylcholanthrene-induced tumors in mice with altered immunological status

Trutin-Ostović

Golubić

Matović

et al. 1986

“…We realize that this cannot be a general conclusion for every situation as T-cells may also be important as effector cells in certain defined tumor systems [5]. Actually this is illustrated by the results of a mathematical analysis of the role of macrophages and lymphocytes in the tumor rejection process.…”

Section: Discussionmentioning

confidence: 97%

The role of host lymphocytes and host macrophages in antitumor reactions after injection of sensitized lymphocytes and tumor target cells into naive mice

Dullens

Vuist

Maas

et al. 1986

DBA/2 mice were immunized i.p. against syngeneic SL2 lymphosarcoma cells. At various days after the last immunization peritoneal and spleen lymphocytes were collected. The lymphocyte suspensions were enriched for T-cells by nylon wool filtration. The peritoneal T-cells from immunized mice (a) expressed direct specific antitumor cytotoxicity in vitro, (b) induced macrophage cytotoxicity in vitro, and (c) exerted tumor neutralization measured in a Winn-type assay. Spleen T-cells from these immunized mice (a) expressed no direct specific antitumor cytotoxicity in vitro, (b) only induced moderate macrophage cytotoxicity in vitro, but (c) exerted tumor neutralization in a Winn assay. For effective tumor neutralization in vivo effector target cell ratios of 1000:1 were required. When the effector/target ratio of 1000:1 was maintained but the absolute numbers of effector and target cells were lowered from 10(6) to 10(5) lymphocytes and 10(3) to 10(2) target cells respectively, no tumor neutralization was obtained. The major effect of the sensitized-transferred T-lymphocytes seemed to be the induction of cytotoxic macrophages in the (naive) recipient mice, as the peritoneal macrophages collected from the recipient mice 7 days after i.p. injection of a mixture of sensitized T-cells and tumor cells were cytotoxic. Purified peritoneal T-lymphocytes collected from these recipient mice were able to induce macrophage cytotoxicity in vitro but expressed no cytotoxic T-cell activity. In conclusion, our results show that in the tumor system used, tumor neutralization after transfer of sensitized lymphocytes is not dependent on the presence of cytotoxic T-lymphocytes. Lymphocytes with the strongest potency to render macrophages cytotoxic (in vitro and in vivo) also induce the best tumor neutralization in vivo, suggesting an important role for host macrophages as antitumor effector cells.

“…In contrast, the observations that athymic nude mice lacking T cell function do not develop many spontaneous tumours and that immunodeficient patients exhibit a very restricted range of neoplasms [3,221 seem to stand against this view. At present, concepts in tumour immunology are changing fundamentally, and there is no need to postulate rather obscure strong immune or natural resistance barriers [4]: if a tumour cell arises de novo, which is considered to be a very infrequent situation [3], it may or may not be attacked by immune or natural resistance mechanisms with their limited potential. However, data to support the idea that these mechanisms induce regression of spontaneously arising tumours do not seem sufficient.…”

Section: Discussionmentioning

confidence: 99%

Increased bleomycin-induced chromosome damage in lymphocytes of patients with common variable immunodeficiency indicates an involvement of chromosomal instability in their cancer predisposition

Vořechovský¹,

Munzarová

Lokaj

1989

To study mutagen-induced chromosome instability in cancer disposition, late S and G2 lymphocytes of 15 patients with common variable immunodeficiency and 14 healthy controls were exposed to bleomycin in vitro. The groups did not differ in the frequency of spontaneous chromosome aberrations. In bleomycin-treated samples we found higher numbers of break events per cell and increased frequency of cells with aberrations compared to the control group. A slightly reduced breakage of chromosome group D was noted in patients. These results support the hypothesis that a higher incidence of cancer in patients with genetically determined immunodeficiencies may be explained by an increased mutagen-induced chromosome instability in at least some of them.