PMID- 30809220
OWN - NLM
STAT- MEDLINE
DCOM- 20191220
LR  - 20200309
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Are Conventional Type 1 Dendritic Cells Critical for Protective Antitumor 
      Immunity and How?
PG  - 9
LID - 10.3389/fimmu.2019.00009 [doi]
LID - 9
AB  - Dendritic cells (DCs) are endowed with a unique potency to prime T cells, as well 
      as to orchestrate their expansion, functional polarization and effector activity 
      in non-lymphoid tissues or in their draining lymph nodes. The concept of 
      harnessing DC immunogenicity to induce protective responses in cancer patients 
      was put forward about 25 years ago and has led to a multitude of DC-based vaccine 
      trials. However, until very recently, objective clinical responses were below 
      expectations. Conventional type 1 DCs (cDC1) excel in the activation of cytotoxic 
      lymphocytes including CD8(+) T cells (CTLs), natural killer (NK) cells, and NKT 
      cells, which are all critical effector cell types in antitumor immunity. Efforts 
      to investigate whether cDC1 might orchestrate immune defenses against cancer are 
      ongoing, thanks to the recent blossoming of tools allowing their manipulation in 
      vivo. Here we are reporting on these studies. We discuss the mouse models used to 
      genetically deplete or manipulate cDC1, and their main caveats. We present 
      current knowledge on the role of cDC1 in the spontaneous immune rejection of 
      tumors engrafted in syngeneic mouse recipients, as a surrogate model to cancer 
      immunosurveillance, and how this process is promoted by type I interferon (IFN-I) 
      effects on cDC1. We also discuss cDC1 implication in promoting the protective 
      effects of immunotherapies in mouse preclinical models, especially for adoptive 
      cell transfer (ACT) and immune checkpoint blockers (ICB). We elaborate on how to 
      improve this process by in vivo reprogramming of certain cDC1 functions with 
      off-the-shelf compounds. We also summarize and discuss basic research and 
      clinical data supporting the hypothesis that the protective antitumor functions 
      of cDC1 inferred from mouse preclinical models are conserved in humans. This 
      analysis supports potential applicability to cancer patients of the 
      cDC1-targeting adjuvant immunotherapies showing promising results in mouse 
      models. Nonetheless, further investigations on cDC1 and their implications in 
      anti-cancer mechanisms are needed to determine whether they are the missing key 
      that will ultimately help switching cold tumors into therapeutically responsive 
      hot tumors, and how precisely they mediate their protective effects.
FAU - Cancel, Jean-Charles
AU  - Cancel JC
AD  - CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living 
      Systems, Aix Marseille University, Marseille, France.
FAU - Crozat, Karine
AU  - Crozat K
AD  - CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living 
      Systems, Aix Marseille University, Marseille, France.
FAU - Dalod, Marc
AU  - Dalod M
AD  - CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living 
      Systems, Aix Marseille University, Marseille, France.
FAU - Mattiuz, Raphael
AU  - Mattiuz R
AD  - CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Turing Center for Living 
      Systems, Aix Marseille University, Marseille, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190212
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Animals
MH  - Antigen-Presenting Cells
MH  - Antigens, Neoplasm/immunology
MH  - Cancer Vaccines/immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - *Immunity
MH  - Immunocompromised Host
MH  - *Immunologic Surveillance
MH  - Immunotherapy
MH  - Neoplasms/*immunology/metabolism/pathology/therapy
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - Tumor Escape/immunology
PMC - PMC6379659
OTO - NOTNLM
OT  - CD8+ T cells
OT  - NK cells
OT  - cancer immunosurveillance
OT  - clinical trials
OT  - conventional type 1 dendritic cells
OT  - immunotherapy
OT  - tumor
OT  - type I IFN
EDAT- 2019/02/28 06:00
MHDA- 2019/12/21 06:00
PMCR- 2019/01/01
CRDT- 2019/02/28 06:00
PHST- 2018/09/30 00:00 [received]
PHST- 2019/01/04 00:00 [accepted]
PHST- 2019/02/28 06:00 [entrez]
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2019/12/21 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.00009 [doi]
PST - epublish
SO  - Front Immunol. 2019 Feb 12;10:9. doi: 10.3389/fimmu.2019.00009. eCollection 2019.