Innate immune recognition of cancer

Annu Rev Immunol. 2015;33:445-74. doi: 10.1146/annurev-immunol-032414-112043. Epub 2015 Jan 22.


The observation that a subset of cancer patients show evidence for spontaneous CD8+ T cell priming against tumor-associated antigens has generated renewed interest in the innate immune pathways that might serve as a bridge to an adaptive immune response to tumors. Manipulation of this endogenous T cell response with therapeutic intent-for example, using blocking antibodies inhibiting PD-1/PD-L1 (programmed death-1/programmed death ligand 1) interactions-is showing impressive clinical results. As such, understanding the innate immune mechanisms that enable this T cell response has important clinical relevance. Defined innate immune interactions in the cancer context include recognition by innate cell populations (NK cells, NKT cells, and γδ T cells) and also by dendritic cells and macrophages in response to damage-associated molecular patterns (DAMPs). Recent evidence has indicated that the major DAMP driving host antitumor immune responses is tumor-derived DNA, sensed by the stimulator of interferon gene (STING) pathway and driving type I IFN production. A deeper knowledge of the clinically relevant innate immune pathways involved in the recognition of tumors is leading toward new therapeutic strategies for cancer treatment.

Keywords: STING; cancer immunotherapy; innate immune sensing; tumor immunity; type I interferons.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Complement System Proteins / immunology
  • Complement System Proteins / metabolism
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immune System / cytology
  • Immunity, Innate*
  • Immunotherapy
  • Ligands
  • Macrophage Activation
  • Macrophages / immunology
  • Macrophages / metabolism
  • Microbiota
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Neoplasms / microbiology
  • Neoplasms / therapy
  • Signal Transduction


  • Ligands
  • Complement System Proteins