Tumour immunity: effector response to tumour and role of the microenvironment.
Substantial evidence shows that inflammation promotes oncogenesis and, occasionally, participates in cancer rejection. This paradox can be accounted for by a dynamic switch from chronic smouldering inflammation promoting cancer-cell survival to florid, tissue-disruptive inflammatory reactions that trigger cancer-cell destruction. Clinical and experimental observations suggest that the mechanism of this switch recapitulates the events associated with pathogen infection, which stimulate immune cells to recognise danger signals and activate immune effector functions. Generally, cancers do not have danger signals and, therefore, they cannot elicit strong immune reactions. Synthetic molecules have been developed that mimic pathogen invasion at the tumour site. These compounds activate dendritic cells to produce proinflammatory cytokines, which in turn trigger cytotoxic mechanisms leading to cancer death. Simultaneously, dendritic cells capture antigen shed by dying cancer cells, undergo activation, and stimulate antigen-specific T and B cells. This process results in massive amplification of the antineoplastic inflammatory process. Thus, although anti-inflammatory drugs can prevent onset of some malignant diseases, induction of T cells specific for tumour antigen by active immunisation, combined with powerful activation signals within the cancer microenvironment, might yield the best strategy for treatment of established cancers.
Mantovani
Alberto
A
Istituto Clinico Humanitas and Institute of Pathology, University of Milan, Milan, Italy.
Romero
Pedro
P
Palucka
A Karolina
AK
Marincola
Francesco M
FM
D000818:Animals; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000502:physiology; D009369:Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology
D000949:Histocompatibility Antigens Class II