Immunosenescence, suppression and tumour progression.
There are good arguments for suggesting that two seminal papers published 50 years ago can be taken as the beginning of modern tumour immunology. These papers by R. Baldwin, "Immunity to transplanted tumour: the effect of tumour extracts on the growth of homologous tumours in rats" and "Immunity to methylcholanthrene-induced tumours in inbred rats following atrophy and regression of the implanted tumours" (Br J Cancer 9:646-51 and 652-657, 1955) showed that once tumours are established, they and their products can be recognised by the adaptive immune system and rejected. However, the tumour normally co-evolves with immunity, like a parasite, rather than being suddenly introduced as in these, and many other, experimental models. Dynamics of this co-evolution are illustrated by findings that inflammation enhances tumorigenicity, yet is important to enable T cells to respond properly to tumour antigen and exert anti-tumour effects. The important thing is to maintain the balance between effective anti-tumour immunity and tumour escape and/or stimulatory mechanisms. Tumours almost always co-exist with immune defence systems over extended periods and interact chronically with T cells. The effect of this is potentially similar to other situations of chronic antigenic stress, particularly lifelong persistent virus infection, most strikingly, CMV infection. The questions briefly explored in this symposium paper are what happens when T lymphocyte clones are chronically stimulated by antigen which is not or cannot be eliminated? What are the similarities and differences between chronic antigenic stimulation by tumour antigen versus CMV antigen? What can we learn in one system which may illuminate the other?
Pawelec
G
G
Center for Medical Research and Department of Immunology, University of Tübingen, Tübingen, Germany. graham.pawelec@uni-tuebingen.de
Koch
S
S
Griesemann
H
H
Rehbein
A
A
Hähnel
K
K
Gouttefangeas
C
C
D000368:Aged; D000818:Animals; D002999:Clone Cells; D003587:Cytomegalovirus / Q000276:immunology*; D018450:Disease Progression; D006801:Humans; D007157:Immunologic Surveillance; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology*