PMID- 26590829
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 65
IP  - 7
DP  - 2016 Jul
TI  - Immune-modulating properties of ionizing radiation: rationale for the treatment 
      of cancer by combination radiotherapy and immune checkpoint inhibitors.
PG  - 779-86
LID - 10.1007/s00262-015-1771-8 [doi]
AB  - Radiotherapy (RT) utilizes the DNA-damaging properties of ionizing radiation to 
      control tumor growth and ultimately kill tumor cells. By modifying the tumor cell 
      phenotype and the tumor microenvironment, it may also modulate the immune system. 
      However, out-of-field reactions of RT mostly assume further immune activation. 
      Here, the sequence of the applications of RT and immunotherapy is crucial, just 
      as the dose and fractionation may be. Lower single doses may impact on tumor 
      vascularization and immune cell infiltration in particular, while higher doses 
      may impact on intratumoral induction and production of type I interferons. The 
      induction of immunogenic cancer cell death seems in turn to be a common mechanism 
      for most RT schemes. Dendritic cells (DCs) are activated by the released danger 
      signals and by taking up tumor peptides derived from irradiated cells. DCs 
      subsequently activate T cells, a process that has to be tightly controlled to 
      ensure tolerance. Inhibitory pathways known as immune checkpoints exist for this 
      purpose and are exploited by tumors to inhibit immune responses. Cytotoxic T 
      lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on T 
      cells are two major checkpoints. The biological concepts behind the findings that 
      RT in combination with anti-CTLA-4 and/or anti-PD-L1 blockade stimulates CD8+ T 
      cell-mediated anti-tumor immunity are reviewed in detail. On this basis, we 
      suggest clinically significant combinations and sequences of RT and immune 
      checkpoint inhibition. We conclude that RT and immune therapies complement one 
      another.
FAU - Derer, Anja
AU  - Derer A
AD  - Department of Radiation Oncology, Universitatsklinikum Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Universitatsstrasse 27, 
      91054, Erlangen, Germany.
FAU - Frey, Benjamin
AU  - Frey B
AD  - Department of Radiation Oncology, Universitatsklinikum Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Universitatsstrasse 27, 
      91054, Erlangen, Germany.
FAU - Fietkau, Rainer
AU  - Fietkau R
AD  - Department of Radiation Oncology, Universitatsklinikum Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Universitatsstrasse 27, 
      91054, Erlangen, Germany.
FAU - Gaipl, Udo S
AU  - Gaipl US
AD  - Department of Radiation Oncology, Universitatsklinikum Erlangen, 
      Friedrich-Alexander-Universitat Erlangen-Nurnberg (FAU), Universitatsstrasse 27, 
      91054, Erlangen, Germany. udo.gaipl@uk-erlangen.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20151121
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Adjuvants, Immunologic)
SB  - IM
MH  - Adjuvants, Immunologic/therapeutic use
MH  - Animals
MH  - Combined Modality Therapy
MH  - Dendritic Cells/immunology/radiation effects
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Neoplasms/drug therapy/*immunology/*radiotherapy/therapy
MH  - Radiation, Ionizing
MH  - T-Lymphocytes/immunology/radiation effects
MH  - Up-Regulation
PMC - PMC11028616
OTO - NOTNLM
OT  - CITIM 2015
OT  - Immune checkpoint inhibitors
OT  - Immunogenic cancer cell death
OT  - Immunotherapy
OT  - Out-of-field effect
OT  - Radiotherapy
COIS- All authors declare that they have no competing interests.
EDAT- 2015/11/23 06:00
MHDA- 2017/03/17 06:00
PMCR- 2015/11/21
CRDT- 2015/11/23 06:00
PHST- 2015/08/30 00:00 [received]
PHST- 2015/10/30 00:00 [accepted]
PHST- 2015/11/23 06:00 [entrez]
PHST- 2015/11/23 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
PHST- 2015/11/21 00:00 [pmc-release]
AID - 10.1007/s00262-015-1771-8 [pii]
AID - 1771 [pii]
AID - 10.1007/s00262-015-1771-8 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2016 Jul;65(7):779-86. doi: 10.1007/s00262-015-1771-8. 
      Epub 2015 Nov 21.