Summary
It has been previously shown that p43 — a breast cancer associated antigen — has immunosuppressive properties. The present study was carried out in order to elucidate the pathomechanisms of immunosuppression in breast cancer patients influenced by the expression of p43. Lymphocytes were cultured from blood of 29 women with benign lesions in the breast as well as from 41 female patients with breast cancer. Lymphocyte stimulation was performed by addition of Concanavalin (Con A) in cultures with lymphocytes alone (CONLYM) or in lymphocytes incubated with p43 (CONAg). In other series immunomodulation was tried by addition of indomethacin (INDLYM, INDAg), levamisole (LEVLYM, LEVAg), or interleukin-2 (ILLYM, ILAG). In breast cancer patients, addition of p43 significantly inhibited the activation of lymphocyte proliferation by Con A compared to women with benign tumors. The addition of indomethacin or levamisole did not influence this inhibitory effect of p43 in breast cancer patients. Contrary to these observations, addition of IL-2 resulted in increased proliferation of lymphocytes from patients with benign as well as malignant tumors, which was inhibited after addition of p43. Analysis of the correlation of the immunosuppressive properties of p43 in correlation with prognostic factors for breast cancer showed evidence for a stronger activity of p43 in early stage tumors (i.e. smaller than 2 cm, lymph node negative, histologic grading GI), confirming previous observations of a higher expression of p43 in early stages of breast cancer.
This is a preview of subscription content, log in via an institution to check access.
References
Moroz C, Giler SH, Kupfer B, Urca I: Lymphocytes bearing surface ferritin in patients with Hodgkin's disease and breast cancer. N Engl J Med 298: 1175–1176, 1977
Moroz C, Bessler H: Ferritin as a marker in malignancy. In: De Sousa M, Brock J (eds) Iron in Immunity, Cancer and Inflammation. Wiley, New York, 1989, pp 283–301
Maymon R, Bahari C, Moroz C: Placental isoferritin measured by a specific monoclonal antibody as a new predictive marker for premature contractions. Obstet Gynecol 74: 597–599, 1989
Hahn HWL, Stahlhut MW, Chung L: Inhibitory effects of isoferritins from tumour and non-tumour tissue on E-rosettes formation. Lancet i: 43–44, 1984
Rosen HR, Stierer M, Göttlicher J, Wolf H, Weber R, Vogl E, Eibl M: Determination of placental ferritin (PLF)-positive lymphocytes in women in early stages of breast cancer. Int J Cancer 52: 229–233, 1992
Whitehead RH, Roberts GP, Thatcher J, Teasdale C, Hughs LE: Masking of receptors for sheep erythrocytes on human T-lymphocytes by sera from breast cancer patients. J Natl Cancer Inst 58: 1573–1577, 1977
Sirota L, Kupfer B, Moroz C: Placental isoferritin as a physiological downregulator of cellular immunoreactivity during pregnancy. Clin Exp Immunol 77: 257–262, 1989
Rosen HR, Ausch C, Reiner G, Reinerova M, Svec J, Tüchler H, Schiessel R, Moroz C: Downregulation of lymphocyte mitogenesis by breast cancer-associated p43. Cancer Lett 82: 105–111, 1994
Bloom HJG, Richardson WW: Histological grading and prognosis in breast cancer. Br J Cancer 11: 359–364, 1957
Stierer M, Rosen H, Weber R, Hanak H, Spona J, Tüchler H: Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. Ann Surg 218: 13–21, 1993
Sedlak J, Reinerova M, Hunakova L, Ausch C, Chorvath B, Rosen H, Moroz C: Alterations of cell surface antigens induced by placental isoform of ferritin in human carcinoma cell lines. Cancer Lett 94: 101–106, 1995
Corty PE, Brando C, Shevach EM: CD59 functions as a signal-transducing molecule for human T cell activation. J Immunol 146: 4092–4096, 1991
Halvorsen R, Gaudernack G, Leivestad T, Varidal F, Thorsby E: Activation of resting pure CD4- and CD8- cells via CD3. Requirements for second signals. Scand J Immunol 26: 197–202, 1987
Halvorsen R, Leivestad T, Gaudernack G, Thorsby E: Accessory cell dependent T cell activation via Ti/CD3; involvement of CD2-LFA3 interactions. Scand J Immunol 28: 277–283, 1988
Hunig T, Tiefenthaler G, Meyer zum Buschenfelde KH, Meuer SC: Alternative pathway activation of T cells by binding of CD2 to its cell surface ligand. Nature 326: 298–291, 1987
Meuer SC, Meyer zum Buschenfelde KH: T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. J Immunol 136: 4106–4110, 1986
Rosen HR, Moroz C, Reiner A, Reinerova M, Stierer M, Svec J, Schemper M, Jakesz R: Placental isoferritin associated p43 antigen correlates with features of high differentiation in breast cancer. Breast Cancer Res Treat 24: 17–26, 1992
Rosen HR, Stierer M, Göttlicher J, Wolf H, Spoula H, Eibl M: Determination of placental ferritin-positive peripheral lymphocytes in early stages of breast cancer. Am J Surg 165: 213–217, 1993
Haynes BP, Fauci AS: Introduction to clinical immunology. In: Brunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin MB, Fauci AS (eds) Harrison's Principles of Internal Medicine. McGraw-Hill Book Company, New York, pp 328–337, 1986
Möller G: Elimination of allogeneic lymphoid cells. Immunol Rev 73: 5–160, 1983
Griffin FM Jr: Mononuclear cell phagocytic mechanisms and host defense. In: Gallin JI, Fauci AS (eds) Advances in Host Defense Mechanisms: Volume I: Phagocytic Cell. Raven Press, New York, pp 31–55, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rosen, H.R., Ausch, C., Reiner, G. et al. Immunosuppression by breast cancer associated p43-effect of immunomodulators. Breast Cancer Res Tr 41, 171–176 (1996). https://doi.org/10.1007/BF01807162
Issue Date:
DOI: https://doi.org/10.1007/BF01807162