Genetics, the Immune Response and Oncogenesis

Abstract

The immune surveillance theory states that a major driving force in the evolution of the immune response has been the necessity to recognize and eliminate clones of neoplastic cells which arise either spontaneously or under the influence of external oncogenic agents. Be it true or false, it is a good theory in that a number of testable predictions derive from it. These include the following: (a) All, or at least the vast majority of neoplastic cells bear altered cell-surface components which can be recognized by the immune system of the primary host; (b) Recognition of the altered cell-surface components leads to mobilization of an immune effector mechanism which eliminates, causes reversion to a non-neoplastic state or causes long-term suppression of the neoplastic cells; (c) Immunosuppression adequate to prevent the rejection of transplanted tumors should lead to decreased latency and increased incidence of spontaneous tumors and of induced tumors following a standard oncogenic insult; (d) Inherent immunodeficiency should be associated with a high incidence of malignancy and a high susceptibility to oncogenesis; and (e) Polymorphic immunoregulatory genes (Ir genes) which influence susceptibility to oncogenesis through regulation of response to tumor-assodated transplantation antigens (TATA) might be expected to exist. The best candidates would probably be genes afEecting susceptibility to specific viral oncogenesis shown to be linked either to the major histocompatibility complex (MHC), or to immunoglobulin heavy chain (Ig-H) allotype. Resistance to oncogenesis would be expected to be dominant over susceptibility.

Effect of Immunologic Intervention on In Vivo Murine Rous Sarcoma Virus Tumorigenesis<xref ref-type="fn" rid="FN2">2</xref>

“…Our observation that tumor incidence can be increased by prolonged immunosuppression with ATS agrees with considerable evidence [reviewed in (16)] that the. incidence of tumors induced in rodents by oncogenic viruses is increased by treatments that impair the generation of T-cell-rriediated immunity.…”

Immunostimulation of the Lymphodependent Phase of Neoplastic Growth

“…Positive, statistically significant reports exist, but they are nonetheless usually of marginal degree (10,11). Failures have also been revealed, and one suspects that many negative results have not been reported (2). Under these circumstances, the real significance of the positive reports remains questionable.…”

How to escape immune surveillance?

“…For example, mice of the H-2 KkIkD k (H-2 k) MHC type respond to poxvirus by generating Kk-restricted but not D k restricted T cells, to lymphocytic choriomeningitis virus by expressing mostly D k but few K k restricted T cells and cannot respond to vesicular stomatitis virus at all [12,26]. It is noteworthy that some of the first examples of MHC-linked susceptibility to disease found were cases of MHC-dependent tumour susceptibility in mice [13,21] and man [7,19,23] 1 . Thus, MHC-antigens (H-2K,I,D; HLA-A,B,D,DR) seem not only to define the T cell effector functions, but because of self-recognition (or restriction), immune responsiveness is influenced profoundly.…”