PMID- 28522749
OWN - NLM
STAT- MEDLINE
DCOM- 20170928
LR  - 20180412
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 77
IP  - 13
DP  - 2017 Jul 1
TI  - Expansion of Tumor-Infiltrating CD8(+) T cells Expressing PD-1 Improves the
      Efficacy of Adoptive T-cell Therapy.
PG  - 3672-3684
LID - 10.1158/0008-5472.CAN-17-0236 [doi]
AB  - Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing
      PD-1 can recognize autologous tumor cells, suggesting that cells derived from
      PD-1(+) TILs can be used in adoptive T-cell therapy (ACT). However, no study thus
      far has evaluated the antitumor activity of PD-1-selected TILs in vivo In two
      mouse models of solid tumors, we show that PD-1 allows identification and
      isolation of tumor-specific TILs without previous knowledge of their antigen
      specificities. Importantly, despite the high proportion of tumor-reactive T cells
      present in bulk CD8 TILs before expansion, only T-cell products derived from
      sorted PD-1(+), but not from PD-1(-) or bulk CD8 TILs, specifically recognized
      tumor cells. The fold expansion of PD-1(+) CD8 TILs was 10 times lower than that 
      of PD-1(-) cells, suggesting that outgrowth of PD-1(-) cells was the limiting
      factor in the tumor specificity of cells derived from bulk CD8 TILs. The highly
      differentiated state of PD-1(+) cells was likely the main cause hampering ex vivo
      expansion of this subset. Moreover, PD-1 precisely identified
      marrow-infiltrating, myeloma-specific T cells in a mouse model of multiple
      myeloma. In vivo, only cells expanded from PD-1(+) CD8 TILs contained tumor
      progression, and their efficacy was enhanced by PDL-1 blockade. Overall, our data
      provide a rationale for the use of PD-1-selected TILs in ACT. Cancer Res; 77(13);
      3672-84. (c)2017 AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Fernandez-Poma, Sarita M
AU  - Fernandez-Poma SM
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Salas-Benito, Diego
AU  - Salas-Benito D
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
AD  - Oncology Department, University Clinic, University of Navarra, Navarra, Spain.
FAU - Lozano, Teresa
AU  - Lozano T
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Casares, Noelia
AU  - Casares N
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Riezu-Boj, Jose-Ignacio
AU  - Riezu-Boj JI
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
AD  - Centre for Nutrition Research, University of Navarra, Navarra, Spain.
FAU - Mancheno, Uxua
AU  - Mancheno U
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Elizalde, Edurne
AU  - Elizalde E
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Alignani, Diego
AU  - Alignani D
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
AD  - Cytometry Unit, CIMA, University of Navarra, Navarra, Spain.
FAU - Zubeldia, Natalia
AU  - Zubeldia N
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Otano, Itziar
AU  - Otano I
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Conde, Enrique
AU  - Conde E
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Sarobe, Pablo
AU  - Sarobe P
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Lasarte, Juan Jose
AU  - Lasarte JJ
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
FAU - Hervas-Stubbs, Sandra
AU  - Hervas-Stubbs S
AD  - Program of Immunology and Immunotherapy, Center for Applied Medical Research
      (CIMA), University of Navarra, Navarra, Spain. mshervas@unav.es.
AD  - Instituto de Investigacion Sanitaria de Navarra (IdISNA), Navarra, Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170518
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Pdcd1 protein, mouse)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Lymphocytes, Tumor-Infiltrating/*immunology
MH  - Melanoma, Experimental/immunology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Programmed Cell Death 1 Receptor/*biosynthesis/immunology
EDAT- 2017/05/20 06:00
MHDA- 2017/09/29 06:00
CRDT- 2017/05/20 06:00
PHST- 2017/01/24 00:00 [received]
PHST- 2017/04/06 00:00 [revised]
PHST- 2017/05/01 00:00 [accepted]
PHST- 2017/05/20 06:00 [pubmed]
PHST- 2017/09/29 06:00 [medline]
PHST- 2017/05/20 06:00 [entrez]
AID - 0008-5472.CAN-17-0236 [pii]
AID - 10.1158/0008-5472.CAN-17-0236 [doi]
PST - ppublish
SO  - Cancer Res. 2017 Jul 1;77(13):3672-3684. doi: 10.1158/0008-5472.CAN-17-0236. Epub
      2017 May 18.