Skip to main content
PMC home page
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1984 Mar;16(3):162–169. doi: 10.1007/BF00205423

Suppression of antitumor immunity by macrophages in spleens of mice bearing a large MOPC-315 tumor

Qing-Wei Ye 1, Margalit B Mokyr 1, Joseph M Pyle 1, Sheldon Dray 1,✉
PMCID: PMC11039285  PMID: 6561068

Abstract

We had shown previously that progression of MOPC-315 plasmacytoma growth is associated with an increase in the percentage of macrophages in the spleen as well as a decrease in the ability of tumor-bearer spleen cells to mount an antitumor cytotoxic response upon in vitro immunization. Here we provide evidence that macrophages in the MOPC-315 tumor-bearer spleen are responsible at least in part for the suppression of the generation of antitumor cytotoxicity. Accordingly, removal of most macrophages by depletion of phagocytic cells or Sephadex G-10-adherent cells from spleens of mice bearing a large tumor resulted in augmented antitumor immune potential. Also, Sephadex G-10-adherent spleen cells from tumor-bearing (but not normal) mice drastically suppressed the in vitro generation of antitumor cytotoxicity by normal spleen cells. The suppressive activity of these adherent cells did not reside in contaminating suppressor T cells, since it was not reduced by treatment with monoclonal anti-Thy 1.2 antibody plus complement. The Sephadex G-10-adherent cell population from the tumor-bearer spleen suppressed the in vitro generation of antitumor cytotoxicity against autochthonous tumor cells but not against allogeneic EL4 tumor cells, and hence the suppression was apparently specific. The suppressive activity of the Sephadex G-10-adherent cell population from tumor-bearer spleens was overcome by treatment of the tumor-bearing mice with a low curative dose of cyclophosphamide. This immunomodulatory effect of a low dose of the drug in overcoming the suppression mediated by the Sephadex G-10-adherent cell population enables the effector arm of the immune system of tumor-bearing mice to cooperate effectively with the drug's tumoricidal activity in tumor eradication.

Keywords: Spleen Cell, Suppressive Activity, Plasmacytoma, Tumoricidal Activity, Normal Spleen

References

  • 1.Baldwin RW, Price MR. Tumor antigens and tumor-host relationships. Annu Rev Med. 1976;27:151. doi: 10.1146/annurev.me.27.020176.001055. [DOI] [PubMed] [Google Scholar]
  • 2.Bluestone JA, Lopez C. Suppression of the immune response in tumor bearing mice. II. Characterization of adherent suppressor cells. J Natl Cancer Inst. 1979;63:1221. [PubMed] [Google Scholar]
  • 3.Braun DP, Harris JE. Relationship of leukocyte numbers, immunoregulatory cell function, and phytohemagglutinin responsiveness in cancer patients. J Natl Cancer Inst. 1981;67:809. [PubMed] [Google Scholar]
  • 4.Brunner KT, Mauel J, Rudolf H, Chapuis B. Studies on autograft immunity in mice. I. Induction, development, and in vitro assay of cellular immunity. Immunology. 1970;18:499. [PMC free article] [PubMed] [Google Scholar]
  • 5.Burton R, Thompson J, Warner NL. In vitro induction of tumor-specific immunity. J Immunol Methods. 1975;8:133. doi: 10.1016/0022-1759(75)90090-3. [DOI] [PubMed] [Google Scholar]
  • 6.Chang ZL, Wang J, Wang QD, Liu KL, Yao Z. Activation of adherent suppressor macrophages in spleen of mice bearing Ehrlich solid tumor. Acta Biologiae Experimentalis Sinica. 1980;13:155. [Google Scholar]
  • 7.Dean JH, Cannon GB, Jerrells TR, McCoy JL, Herberman RB. Sensitive parameters for general measurements of immunocompetence and antitumor reactivity in lung cancer patients and possible mechanisms of immunosuppression. In: Crispen RG, editor. Cancer immunotherapy: Experimental and clinical, vol 3. Amsterdam: Elsevier/North-Holland; 1980. p. 357. [Google Scholar]
  • 8.Elgert KD, Farrar WL. Suppressor cell activity in tumor-bearing mice. I. Dualistic inhibition by suppressor T lymphocytes and macrophages. J Immunol. 1977;120:1345. [PubMed] [Google Scholar]
  • 9.Fujimoto S, Greene MI, Sehon AH. Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976;116:800. [PubMed] [Google Scholar]
  • 10.Garrigues HJ, Romero P, Hellstrom I, Hellstrom KE. Adherent cells (macrophages?) in tumor-bearing mice suppress MLC responses. Cell Immunol. 1981;60:109. doi: 10.1016/0008-8749(81)90252-5. [DOI] [PubMed] [Google Scholar]
  • 11.Glaser M, Kirchner H, Herberman RB. Inhibition of in vitro lymphoproliferative responses to tumor-associated antigens by suppressor cells from rats bearing progressively growing Gross leukemia virus-induced tumors. Int J Cancer. 1975;16:384. doi: 10.1002/ijc.2910160305. [DOI] [PubMed] [Google Scholar]
  • 12.Hellstrom KE, Hellstrom I. Lymphocyte-mediated cytotoxicity and blocking serum activity to tumor antigens. Adv Immunol. 1974;18:209. doi: 10.1016/s0065-2776(08)60311-9. [DOI] [PubMed] [Google Scholar]
  • 13.Hellstrom KE, Hellstrom I, Nepom J. Specific blocking factors: are they important? Biochim Biophys Acta. 1977;473:121. doi: 10.1016/0304-419x(77)90003-8. [DOI] [PubMed] [Google Scholar]
  • 14.Hengst JCD, Mokyr MB, Dray S. Importance of timing in cyclophosphamide therapy of MOPC-315 tumor-bearing mice. Cancer Res. 1980;40:2135. [PubMed] [Google Scholar]
  • 15.Hoover RG, Dieckgraefe BK, Lake J, Kemp JD, Lynch RG. Lymphocyte surface membrane immunoglobulin in myeloma. III. IgA plasmacytomas induce large numbers of circulating, adult-thymectomy-sensitive, θ+, Lyt-1− 2+ lymphocytes with IgA-Fc receptors. J Immunol. 1982;129:2329. [PubMed] [Google Scholar]
  • 16.Hoover RG, Gebel HM, Dieckgraefe BK, Hickman S, Rebbe NF, Hirayama N, Ovary Z, Lynch RG. Occurrence and potential significance of increased numbers of T cells with Fc receptors in myeloma. Immunol Rev. 1981;56:115. doi: 10.1111/j.1600-065x.1981.tb01049.x. [DOI] [PubMed] [Google Scholar]
  • 17.Jerrells TR, Dean JH, Richardson GL, McCoy JL, Herberman RB. Role of suppressor cells in depression of in vitro lymphoproliferative responses of lung cancer and breast cancer patients. J Natl Cancer Inst. 1978;61:1001. [PubMed] [Google Scholar]
  • 18.Kenmarch J, Zolla-Pozner S. Origin and function of suppressor macrophages in myeloma. J Immunol. 1980;124:268. [PubMed] [Google Scholar]
  • 19.Kirchner H, Chused TM, Herberman RB, Holden HT, Lavrin DH. Evidence of suppressor cell activity in spleen of mice bearing primary tumors induced by moloney sarcoma virus. J Exp Med. 1974;139:1473. doi: 10.1084/jem.139.6.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Koski IR, Poplack DG, Blaese RM. A non-specific esterase stain for the identification of monocytes and macrophages. In: Bloom BR, David JR, editors. In vitro methods in cell-mediated tumor immunity. New York: Academic Press; 1977. p. 359. [Google Scholar]
  • 21.Kruisbeek AM, Van Hees M. Role of macrophages in the tumor-induced suppression of mitogen responses in rats. J Natl Cancer Inst. 1977;58:1653. doi: 10.1093/jnci/58.6.1653. [DOI] [PubMed] [Google Scholar]
  • 22.Ledbetter JA, Herzenberg LA. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  • 23.Ly IA, Mishell RI. Separation of mouse spleen cells by passage through column of Sephadex G-10. J Immunol Methods. 1974;5:239. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  • 24.Mokyr MB, Braun DP, Dray S. Augmentation of antitumor cytotoxicity in MOPC-315 tumor bearer spleen cells by depletion of glass-adherent cells prior to in vitro activation. Cancer Res. 1979;39:785. [PubMed] [Google Scholar]
  • 25.Mokyr MB, Braun DP, Usher D, Reiter H, Dray S. The development of in vitro and in vivo antitumor cytotoxicity in noncytotoxic, MOPC-315 tumor-bearer spleen cells ‘educated’ in vitro with MOPC-315 tumor cells. Cancer Immunol Immunother. 1978;4:143. [Google Scholar]
  • 26.Mokyr MB, Hengst JCD, Przepiorka D, Dray S. Augmentation of antitumor cytotoxicity of MOPC-315 tumor-bearer spleen cells by depletion of dinitrophenol-adherent cells prior to in vitro immunization. Cancer Res. 1979;39:3928. [PubMed] [Google Scholar]
  • 27.Naor D. Suppressor cells: Permitters and promoters of malignancy. Adv Cancer Res. 1979;29:45. doi: 10.1016/s0065-230x(08)60846-5. [DOI] [PubMed] [Google Scholar]
  • 28.Plata F, MacDonald HR, Shain B. Suppressor T cells regulate the cytolytic T lymphocyte response to syngeneic tumors induced by murine sarcoma virus (MSV) in the mouse. J Immunol. 1979;123:852. [PubMed] [Google Scholar]
  • 29.Rosenstreich DL, Blake JT, Rosenthal AS. The peritoneal exudate lymphocyte I. Differences in antigen responsiveness between exudate and lymph node lymphocytes from immunized guinea pigs. J Exp Med. 1971;134:1170. doi: 10.1084/jem.134.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Ting CC, Hargrove ME. Tumor cell-triggered macrophage-mediated suppression of the T-cell cytotoxic response to tumor-associated antigens. J Natl Cancer Inst. 1982;69:873. [PubMed] [Google Scholar]
  • 31.Ting CC, Rodrigues D. Tumor cell-triggered macrophage-mediated suppression and T-cell cytotoxic response to tumor-associated antigens. I. Characterization of the cell components of suppression. J Natl Cancer Inst. 1982;69:867. [PubMed] [Google Scholar]
  • 32.Tracey DE. The requirement of macrophage in the augmentation of natural killer cell activity by BCG. J Immunol. 1979;123:840. [PubMed] [Google Scholar]
  • 33.Twomey JJ, Laughter AH, Farrow S, Douglas CD. Hodgkin's disease. An immunodepleting and immunosuppressive disorder. J Clin Invest. 1975;56:467. doi: 10.1172/JCI108113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Webb PJ, Brooks CG, Baldwin RW. Macrophage-like suppressor cells in rats. II. Evidence for a quantitative rather than a qualitative change in tumor-bearer animals. Cell Immunol. 1980;52:381. doi: 10.1016/0008-8749(80)90359-7. [DOI] [PubMed] [Google Scholar]
  • 35.Webb DR, Nowowiejski I. Control of suppressor cell activation via endogenous prostaglandin synthesis: The role of T cells and macrophages. Cell Immunol. 1981;63:321. doi: 10.1016/0008-8749(81)90011-3. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES