Differential induction of natural suppressor activity of bone marrow cellsin vitro by different types of tumors

Abstract

The suppressor activity of bone marrow cells not adhering to plastic is shown to appreciably increase after their 48-hour joint preincubation with mastocytoma P-815 supernatant or WEHI-3 myelomonocytic strain and to be unchanged after incubation with supernatants of K-2 erythroleukemic strain or Ehrlich's ascitic carcinoma. P-815, WEHI-3, and K-2 tumors are shown to produce factors characterized by colony-stimulating activity. Key Words: suppressor cells; tumor; colony-stimulating activityThe so-called natural suppressor cells (NSC) in the bone marrow (BM) are known to inhibit the proliferation of immunocompetent and tumor ceils in vitro by releasing a soluble suppressive factor [5][6][7]10] and in vivo [3,6]. NSC do not possess markers of mature immunoeompetent cells and belong to the BM fraction not adhering to plastic [1]. Experiments with different tumor growth models have shown that the development of a malignant process goes along with an appreciable activation of bone marrow NSC [3,4,6,9,13] and their appearance in the spleen [10,13]. Activation of these cells is associated with the direct influence of colonystimulating factors produced by tumors of many types [14]. Co-incubation of granuloeyte-maerophagal colony-stimulating factor (GM-CSF) or interleukin-3 with normal murine BM cells sharply increases the activity of NSC [12,14]. Tumors are known to vary in their ability to activate bone marrow NSC in vitro. For example, cocultivation of Lewis' pulmonary adenocarcinoma supernatant The purpose of this work was to study the suppressor-inducing and colony-stimulating activities of the factors produced in vitro by different types of tumor eeUs. MATERIALS AND METHODSExperiments were carded out with BALB/c and DBA/2 mice aged 2 to 3 months bred at the Research Laboratory for Experimental Biomedical Simulation, Tomsk Research Center, Russian Academy of Medical Sciences. Ehrlich's adenocarcinoma (in BALB/c mice) and P-815 mastocytoma (in DBA/2 mice) were induced by an intraperitoneal graft of 2x106 tumor cells. K-2 and WEHI-3 cell lines were maintained in vitro in complete culture medium.Cells were cultured in RPMI-1640 medium containing 2 mM HEPES buffer, 2 mM L-glutamine, 10% fetal calf serum (Flow), 5x10 -5 M 2-mercaptoethanol (Fluka), 100 U/ml penicillin, and 100 ~tg/ml streptomycin.

Activated lymphocytes produce mediators potentiating the antitumor cytostatic activity of bone marrow cells

“…Bone marrow cells (BMC) phenotypically similar to bone marrow natural suppressor cells inhibit the growth of leukemic cells in vitro [1,2,[8][9][10]. Tumor growth suppression by BMC is not associated with tumor cell destruction and is mediated, at least partially, by solutile cytostatic products [9].…”

Production of transmitters stimulating antitumor cytostatic activity of bone marrow cells by activated lymphocytes

“…Bone marrow cells (BMC) similar by many phenotypical signs to bone marrow natural suppressor cells suppress the growth of leukemic cells in vitro [1,2,[8][9][10]. Tumor growth suppression by BMC does not involve tumor cells destruction and is mediated, at least partially, by soluble cytostatic products [9].…”

Suppressive activity of bone marrow cells from patients with stomach cancer. Effect of prostaglandins, transforming growth factor-β, and nitric oxide

“…Some authors attribute immunosuppression in cancer patients to activation of suppressor cells, primarily T suppressors and monocytes [I1]. On the other hand, bone marrow can be a source of suppressor cells in tumor process [ 1,2,10,12]. Bone marrow-derived suppressor cells, immature myeloid precursors have been found in the spleen of cancer patients and even .in the tumor [13].…”