Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells

Immunity. 2013 Apr 18;38(4):729-41. doi: 10.1016/j.immuni.2013.03.003. Epub 2013 Apr 4.

Abstract

The therapeutic efficacy of anthracyclines relies on antitumor immune responses elicited by dying cancer cells. How chemotherapy-induced cell death leads to efficient antigen presentation to T cells, however, remains a conundrum. We found that intratumoral CD11c(+)CD11b(+)Ly6C(hi) cells, which displayed some characteristics of inflammatory dendritic cells and included granulomonocytic precursors, were crucial for anthracycline-induced anticancer immune responses. ATP released by dying cancer cells recruited myeloid cells into tumors and stimulated the local differentiation of CD11c(+)CD11b(+)Ly6C(hi) cells. Such cells efficiently engulfed tumor antigens in situ and presented them to T lymphocytes, thus vaccinating mice, upon adoptive transfer, against a challenge with cancer cells. Manipulations preventing tumor infiltration by CD11c(+)CD11b(+)Ly6C(hi) cells, such as the local overexpression of ectonucleotidases, the blockade of purinergic receptors, or the neutralization of CD11b, abolished the immune system-dependent antitumor activity of anthracyclines. Our results identify a subset of tumor-infiltrating leukocytes as therapy-relevant antigen-presenting cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anthracyclines / administration & dosage*
  • Anthracyclines / adverse effects
  • Antigen-Presenting Cells / immunology*
  • Antigens, Ly / metabolism
  • Antigens, Neoplasm / immunology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Apoptosis
  • CD11b Antigen / metabolism
  • CD11c Antigen / metabolism
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dendritic Cells / immunology*
  • Granulocyte Precursor Cells / immunology
  • Immunity, Cellular
  • Mice
  • Mice, Inbred C57BL
  • Monocyte-Macrophage Precursor Cells / immunology
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / immunology*
  • Nucleotidases / metabolism
  • Receptors, Purinergic / metabolism

Substances

  • Anthracyclines
  • Antigens, Ly
  • Antigens, Neoplasm
  • Antineoplastic Agents
  • CD11b Antigen
  • CD11c Antigen
  • Ly-6C antigen, mouse
  • Receptors, Purinergic
  • Nucleotidases