Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment

Front Immunol. 2018 Dec 20:9:3059. doi: 10.3389/fimmu.2018.03059. eCollection 2018.

Abstract

Dendritic cells (DCs) play a central role in the regulation of the balance between CD8 T cell immunity vs. tolerance to tumor antigens. Cross-priming, a process which DCs activate CD8 T cells by cross-presenting exogenous antigens, plays a critical role in generating anti-tumor CD8 T cell immunity. However, there are compelling evidences now that the tumor microenvironment (TME)-mediated suppression and modulation of tumor-infiltrated DCs (TIDCs) impair their function in initiating potent anti-tumor immunity and even promote tumor progression. Thus, DC-mediated cross-presentation of tumor antigens in tumor-bearing hosts often induces T cell tolerance instead of immunity. As tumor-induced immunosuppression remains one of the major hurdles for cancer immunotherapy, understanding how DCs regulate anti-tumor CD8 T cell immunity in particular within TME has been under intensive investigation. Recent reports on the Batf3-dependent type 1 conventional DCs (cDC1s) in anti-tumor immunity have greatly advanced our understanding on the interplay of DCs and CD8 T cells in the TME, highlighted by the critical role of CD103+ cDC1s in the cross-priming of tumor antigen-specific CD8 T cells. In this review, we will discuss recent advances in anti-tumor CD8 T cell cross-priming by CD103+ cDC1s in TME, and share perspective on future directions including therapeutic applications and memory CD8 T cell responses.

Keywords: CD103+ cDC1s; CD8 T cell immunity; anti-tumor immunity; cancer immunotherapy; cross-priming; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / immunology
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication / immunology*
  • Cross-Priming / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Immunotherapy / methods
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Repressor Proteins / metabolism
  • Tumor Escape / immunology
  • Tumor Microenvironment / immunology*

Substances

  • Antigens, Neoplasm
  • BATF3 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Repressor Proteins