PMID- 35184967
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220616
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 41
IP  - 5
DP  - 2022 May
TI  - Establishment of operational tolerance to sustain antitumor immunotherapy.
PG  - 568-577
LID - S1053-2498(22)00037-7 [pii]
LID - 10.1016/j.healun.2022.01.019 [doi]
AB  - BACKGROUND: Commonly used immunosuppressive drugs are efficacious in the 
      prevention of transplanted solid organ rejection but, are complicated by an 
      increased rate of malignancies. Treatment of the latter with cancer immunotherapy 
      is frequently associated with increased graft loss from rejection. METHODS: B16 
      melanoma was inoculated subcutaneously (s.c.) in the ear of host B6 mice carrying 
      a heterotopic allogenic murine heart. Intratumoral (i.t.) immunotherapy with 
      anti-programmed death-1 (PD-1) and a toll-like receptor 9 (TLR9) agonist was 
      conducted to treat cancer. Cyclosporine A (CsA) therapy or replaced by other 
      immunosuppressive agents was conducted to preserve heart allograft tolerance, 
      respectively. RESULTS: Here we show that long-term allograft-bearing mice 
      receiving CsA therapy and challenged with host-type melanoma resist cancer 
      immunotherapy and reject their grafts after CsA withdrawal. However, when CsA 
      therapy is replaced by intermittent administration of the PI4KIIIbeta inhibitor 
      UCB9608, effective antitumor immunity is induced while preserving graft 
      tolerance. UCB9608 switch combined with i.t. immunotherapy resulted in 
      donor-specific tolerance with preserved third-party responses. This operational 
      tolerance may not be dependent on regulatory T cells (Tregs). CONCLUSIONS: Immune 
      effects induced by UCB9608 switch following CsA therapy allow for antitumor 
      immunity, opening up new approaches to establish donor-specific operational 
      tolerance in solid organ transplantation with cancer.
CI  - Copyright (c) 2022 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Dang, Nana
AU  - Dang N
AD  - Laboratory of Molecular Immunology, Department ;of Microbiology, Immunology and 
      Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
FAU - Waer, Mark
AU  - Waer M
AD  - Laboratory of Molecular Immunology, Department ;of Microbiology, Immunology and 
      Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
FAU - Sprangers, Ben
AU  - Sprangers B
AD  - Laboratory of Molecular Immunology, Department ;of Microbiology, Immunology and 
      Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium; 
      Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.
FAU - Lin, Yuan
AU  - Lin Y
AD  - Laboratory of Molecular Immunology, Department ;of Microbiology, Immunology and 
      Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium. 
      Electronic address: yuan.linphd@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220131
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Immunosuppressive Agents)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
MH  - Animals
MH  - *Cyclosporine/therapeutic use
MH  - Graft Rejection/prevention & control
MH  - Graft Survival
MH  - *Heart Transplantation
MH  - Humans
MH  - Immune Tolerance
MH  - Immunosuppressive Agents/therapeutic use
MH  - Immunotherapy
MH  - Mice
MH  - Rats
MH  - Rats, Inbred Lew
OTO - NOTNLM
OT  - allograft tolerance
OT  - antitumor immunity
OT  - cancer immunotherapy
OT  - heart transplantation
OT  - regulatory T cells
EDAT- 2022/02/22 06:00
MHDA- 2022/04/27 06:00
CRDT- 2022/02/21 05:37
PHST- 2021/08/05 00:00 [received]
PHST- 2021/12/31 00:00 [revised]
PHST- 2022/01/19 00:00 [accepted]
PHST- 2022/02/22 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/02/21 05:37 [entrez]
AID - S1053-2498(22)00037-7 [pii]
AID - 10.1016/j.healun.2022.01.019 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2022 May;41(5):568-577. doi: 
      10.1016/j.healun.2022.01.019. Epub 2022 Jan 31.