Cancer immunosuppression and autoimmune disease: beyond immunosuppressive networks for tumour immunity

Immunology. 2006 Oct;119(2):254-64. doi: 10.1111/j.1365-2567.2006.02430.x.


Cancer immunosuppression evolves by constitution of an immunosuppressive network extending from a primary tumour site to secondary lymphoid organs and peripheral vessels and is mediated by several tumour-derived soluble factors (TDSFs) such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF). TDSFs induce immature myeloid cells and regulatory T cells in accordance with tumour progression, resulting in the inhibition of dendritic cell maturation and T-cell activation in a tumour-specific immune response. Tumour cells grow by exploiting a pro-inflammatory situation in the tumour microenvironment, whereas immune cells are regulated by TDSFs during anti-inflammatory situations--mediated by impaired clearance of apoptotic cells--that cause the release of IL-10, TGF-beta, and prostaglandin E2 (PGE2) by macrophages. Accumulation of impaired apoptotic cells induces anti-DNA antibodies directed against self antigens, which resembles a pseudo-autoimmune status. Systemic lupus erythematosus is a prototype of autoimmune disease that is characterized by defective tolerance of self antigens, the presence of anti-DNA antibodies and a pro-inflammatory response. The anti-DNA antibodies can be produced by impaired clearance of apoptotic cells, which is the result of a hereditary deficiency of complements C1q, C3 and C4, which are involved in the recognition of phagocytosis by macrophages. Thus, it is likely that impaired clearance of apoptotic cells is able to provoke different types of immune dysfunction in cancer and autoimmune disease in which some are similar and others are critically different. This review discusses a comparison of immunological dysfunctions in cancer and autoimmune disease with the aim of exploring new insights beyond cancer immunosuppression in tumour immunity.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Autoimmune Diseases / immunology*
  • Humans
  • Immune Tolerance*
  • Immunotherapy / methods
  • Lupus Erythematosus, Systemic / immunology
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy