Activation of lymphocyte anti-tumour responses in man: effector heterogeneity and the search for immunomodulators.
Data continues to accumulate on the immunological reaction against solid human cancers. The evidence at the present time supports the view that rather than being immunologically invisible, tumour cell antigens are recognised by at least three lymphocyte subsets. Helper T cells can be induced to proliferate upon exposure to cells of the autologous tumour and to secrete detectable levels of interleukin 2 (IL-2). Cultured T cell lines and clones can be shown to respond in primed lymphocyte tests not only to autologous tumour cells but also to allogeneic tumour cells of the same histology and anatomic location. Cytotoxic T cells manifest specific reactivity against cells of the autologous tumour which is distinguishable from natural killing (NK) on the basis of specificity and organ distribution. Natural killer cells can lyse freshly isolated autologous tumour cells after purification on Percoll gradients or when activated by IL-2. There is thus a demonstrable heterogeneity of response to human cancer in unseparated lymphocyte populations and at the clonal level. In limiting dilution assays lymphocytes at the tumour site respond more frequently to autologous tumour relative to NK targets. For at least some tumours there is evidence that the expression of auto-tumour reactivity but not NK correlates with the clinical course of the disease and is a favourable prognostic indicator. The finding of these auto-tumour reactivities has important implications for the search for immunomodulating drugs for cancer treatment. However, it must be recognised that the response is heterogeneous and that the immune system comprises multiple interactive elements that exhibit both positive and negative control. Any treatment modality must take this into account and seek to focus on specific activation of the tumour lytic populations or the inhibition of negative regulatory elements as opposed to seeking a more general augmentation of immune reactivity which may, by stimulating suppressor cells, have a counterproductive effect.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D002999:Clone Cells; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic