Summary
A hypothesis greatly influencing thinking and experimental work in tumor immunology is that many tumor cells arise daily in an organism. However, relatively low numbers of tumours become clinically manifest. This discrepancy has intially led to the hypothesis that the great majority of these potential tumors is killed by immune surveillance mechanisms. After some time, however, serious objections were raised against this function of the immune system. When the interest in immune surveillance faded away, investigators started to study natural resistance against the de novo arising tumor cells. In this paper the data on natural resistance (and immune surveillance) are reviewed. These data lead to the conclusion than an efficient natural resistance that could kill many de novo arising tumor cells is lacking. Taken together the data suggest that no tumors arise when immune surveillance and/or natural resistance are absent. This implies that tumor cells probably do not arise frequently. Acceptance of this conclusion leads to a reappraisal of the role of immune surveillance and natural resistance against tumor cells. This reappraisal will mean a shift from (a) the hypothesized failsafe mechanisms to (b) mechanisms that may or may not kill rarely arising tumor cells, depending for instance on the antigenicity of the tumor cells and their sensitivity to tumoricidal mechanisms.
Similar content being viewed by others
References
Abo T, Miller CA, Gartland CL, Balch CM (1983) Differentiation stages of human natural killer cells in lymphoid tissue from fetal to adult life. J Exp Med 157:273
Baldwin RW (1981) Immunotherapy of cancer. Cancer Chemother Ann 3:178
Bauer KH (1928) Mutationstheorie der Geschwulst-Entstehung. Übergang von körperzellen in Geschwulstzellen durch Genänderung. Springer, Berlin
Becker S, Kiessling R, Lee N, Klein G (1978) Modulation of sensitivity to natural killer cell lysis after in vitro explantation of a mouse lymphoma. J Natl Cancer Inst 61:1495
Burdette WJ (1955) The significance of mutation in relation to the origin to tumor: A review. Cancer Res 15:201
Burnett FM (1971) Immunological surveillance in neoplasia. Transplant Rev 7:3
Chee DO, Townsend CM, Galbraith MA, Eiber FR, Morton DL (1978) Selective reduction of human tumor cell populations by human granulocytes in vitro. Cancer Res 38:4534
Dent PB, Fish LA, White JG, Good RA (1966) Chediak Higashi syndrome. Observations on the nature of the associated malignancy. Lab Invest 15:1634
Dvorak AM, Galli SJ, Galli AS, Hammond ME, Churchill WH, Dvorak HF (1979) Tumor-basophil interactions in vitro — A scanning and transmission electron microscopic study. J Immunol 122:2447
Farram E, Nelson DS (1980) Mouse mast cells as antitumor effector cells. Cell Immunol 55:294
Folkman J, (1976). The vascularization of tumors. Sci Am 234/5:58
Henderson WR, Chi EY, Jong EC, Klebanoff SJ (1981) Mast cell-mediated tumor cell cytotoxicity: Role of the peroxidase system. J Exp Med 153:520
Herberman RB (1980) Natural cell-mediated immunity against tumors. Academic, London
Hibbs JB (1974) Discrimination between neoplastic and non-neoplastic cells in vitro by activated macrophages. J Natl Cancer Inst 53:1487
Kaplan AM, Morahan PS, Regelson W (1974) Induction of macrophage-mediated tumor-cell cytotoxicity by pyran copolymer. J Natl Cancer Inst 52:1919
Keller R (1974) Modulation of cell proliferation by macrophages: a possible function apart from cytotoxic tumor rejection. Br J Cancer 30:401
Klein G, Klein E (1977) Rejectability of virus-induced tumors and non-rejectability of spontaneous tumors: A lesson in contrasts. Transplant Proc 9:1095
Korec S, Herberman RB, Dean HJ, Cannon GB (1980) Cytostasis of tumor cell lines by human granulocytes. Cell Immunol 53:104
Louis CJ (1978) Tumors: Basic principles and clinical aspects. Churchill Livingstone, Edinburgh
Mantovani A, Tagliabue A, Dean J, Jerrels TR, Herberman RB (1979) Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts. Int J Cancer 23:28
Martin WJ, Martin SE (1974) Naturally occurring cytotoxic anti-tumor antibodies in sera of congenically athymic (nude) mice. Nature 249:564
Meltzer MS, Tucker RW, Breuer AC (1975) Interaction of BCG-activated macrophages with neoplastic cell lines in vitro: Cinemicrographic analysis. Cell Immunol 17:30
Minato M, Bloom BR, Jones C, Holland J, Reid LM (1979). Mechanism of rejection of virus persistently infected cells by athymic nude mice. J Exp Med 149:1117
Nehlsen SL (1971) Prolonged administration of antithymocyte serum in mice. I: Observations on cellular and humoral immunity. Clin Exp Immunol 9:63
Outzen HC, Custer RP, Eaton GJ, Prehn RT (1975) Spontaneous and induced tumor incidence in germ-free nude mice. J Reticuloendothel Soc 17:1
Pels E, Den Otter W (1979) Natural cytotoxic macrophages in the peritoneal cavity of mice. Br J Cancer 40:856
Penn I, Halgrimson CG, Starzl TE (1971) De novo malignant tumors in organ transplant recipients. Transplant Proc 3:773
Piessens WF, Churchill WH, David JR (1975) Macrophages activated in vitro with lymphocyte mediators kill neoplastic but not normal cells. J Immunol 114:293
Prehn RT (1976) Do tumors grow because of the immune response of the host? Transplant Rev 28:34
Roder J, Duwe A (1979) The beige mutation in the mouse selectively imparts natural killer cell function. Nature 278:451
Roder JC, Haliotis T (1980) Do NK cells play a role in antitumor surveillance? Immunol Today 1:96
Roder JC, Kiessling R (1978) Target-effector interaction in the natural killer cell system. I: Covariance and genetic control of cytolytic and target cell binding subpopulations in the mouse. Scand J Immunol 8:135
Roder JC, Laing L, Haliotis T (1982) In: Herberman RB (ed) NK cells: fundamental aspects and role in cancer. North Holland, Amsterdam (Human cancer immunology, vol 6)
Rygaard J, Povlsen CO (1976) The nude mouse vs hypothesis of immunological surveillance. Transplant Rev 28:43
Saksela RB, Timonen T (1980) Morphology and surface properties of human NK cells. In: Herbermann RB (ed) Natural cell-mediated immunity against tumors. Academic, London
Salmon JC, Cream-Goldberg N, Lynch NR (1980) Cancer induction by methylcholanthrene and metastatic spread of transplantable tumor in Chediak Higashi (beige mice). Cancer Immunol Immunother 8:67
Sanford BH, Kohn HI, Daly JJ, Soo SF (1973) Long-term spontaneous tumor incidence in neonatally thymectomized mice. J Immunol 110:1437
Stern C (1973) Principles of human genetics. Freeman, San Francisco
Stutman O (1974) Tumor development after 3-methylcholanthrene in immunologically deficient athymic-nude mice. Science 183:534
Sullivan JL, Byron KS, Brewster FE, Purtilo DT (1980) Deficient natural killer cell activity in X-linked lymphoproliferative syndrome. Science 210:543
Talmadge JE, Meyers KM, Prieur DJ, Starkey JR (1980) Role of NK cells in tumor growth and metastasis in beige mice. Nature 284:622
Takasugi M, Akira D, Kinoshita K (1975) Ganulocytes as effectors in cell-mediated cytotoxicity of adherent target cells. Cancer Res 35:2169
Timonen T, Ortaldo JR, Herberman RB (1981) Characteristics of human larger granular lymphocytes and relationship to natural killer and K cells. J. Exp. Med. 153:569
Van Furth R (1980) Cells of the mononuclear phagocyte system. Nomenclature in terms of sites and conditions. In: Van Furth R (ed) Mononuclear phagocytes, part I. Nijhoff The Hague
Vánky F, Argov S, Einhorn S, Klein E (1980) Role of alloantigens in natural killing: allogeneic but not autologous tumor biopsy cells are sensitive for interferon induced cytotoxicity of human blood lymphocytes. J Exp Med 151:1151
Vose BM, Moore M (1980) Natural cytotoxicity in humans: susceptibility of freshly isolated tumor cells to lysis. J Natl Cancer Inst 65:257
Yogeeswaran G, Welsh RM, Gronberg A, Kiessling R, Patarroyo M, Klein G., Gidlund M, Wigzell H, Nilsson K (1982) Surface sialic acid of tumor cells inversely correlates with susceptibility to natural killer cell mediated lysis. In: Herberman RB (ed) NK cells and other natural effector cells. Academic, London
Yong WW, Durdik JM, Urdal D, Hakomori SI, Henney CS (1981) Glycolipid expression in lymphoma cell variants: chemical quantity, immunologic reactivity and correlations with susceptibility to NK cells. J Immunol 126:1
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Den Otter, W. Tumor cells do not arise frequently. Cancer Immunol Immunother 19, 159–162 (1985). https://doi.org/10.1007/BF00199220
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00199220