title: Response of the immune system of mammary tumor-bearing rats to cyclophosphamide and soluble low-molecular-mass tumor-associated antigens: the bone marrow and thymus.
abstract: We showed in a previous study that soluble low-molecular-mass tumor-associated antigens (sTAA) promote the anti-tumor effect of the anticancer drug cyclophosphamide (CPA) on rat mammary carcinogenesis. In this report, we analyzed the possible mechanism underlying this phenomenon. Studies were performed on the bone marrow and thymus from the following groups of rats: i) control rats, ii) rats treated with sTAA, iii) rats treated with CPA, iv) rats treated with CPA and sTAA. The cellular content of the bone marrow and thymus (CD4+ and CD8+ lymphocytes) was analyzed morphometrically and immunohistochemically. In the bone marrow, CPA caused significant substitution of cellular components with fatty tissue whereas sTAA repaired this process. We found that CPA affects mainly the process of myelogenesis whereas sTAA protect the production of lymphocytes. In the thymus, CPA alone or in combination with sTAA repaired the inhibition effect of DMBA on synthesis of CD4+ and CD8+ thymocytes. sTAA further increased the amount of CD8+ T lymphocytes in the medulla of the thymus. Data in the literature as well as the findings presented here demonstrate that the tested treatment, including vaccination with sTAA, actively promotes the generation of the host's antitumor immune response.
authors.affiliation: Laboratory of Experimental Medicine affiliated to the Institute of Pathology, Assaf Harofeh Medical Center, Tserifin, Israel.
authors.forename: Herzl
authors.initials: H
authors.lastname: Ben-Hur
authors.forename: George
authors.initials: G
authors.lastname: Kossoy
authors.forename: Nadja
authors.initials: N
authors.lastname: Kossoy
authors.forename: Itshak
authors.initials: I
authors.lastname: Zusman
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology*; D051381:Rats; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide