PMID- 35191474
OWN - NLM
STAT- MEDLINE
DCOM- 20220415
LR  - 20230825
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 28
IP  - 8
DP  - 2022 Apr 14
TI  - Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid 
      Structures as Correlates of Impaired Cancer Immunosurveillance.
PG  - 1712-1723
LID - 10.1158/1078-0432.CCR-21-3746 [doi]
AB  - PURPOSE: An increased risk to develop cancer is one of the most challenging 
      negative side effects of long-term immunosuppression in organ transplant 
      recipients and impaired cancer immunosurveillance is assumed as underlying 
      mechanism. This study aims to elucidate transplant-related changes in the tumor 
      immune microenvironment (TME) of cancer. EXPERIMENTAL DESIGN: Data from 123 organ 
      transplant recipients (kidney, heart, lung, and liver) were compared with 
      historic data from non-immunosuppressed patients. Digital image analysis of 
      whole-section slides was used to assess abundance and spatial distribution of T 
      cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. 
      Expression of programmed cell death 1 ligand 1 (PD-L1) and 
      human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays. 
      RESULTS: We found a remarkably reduced immune infiltrate in the center tumor (CT) 
      regions as well as the invasive margins (IM) of post-transplant cancers. These 
      differences were more pronounced in the IM than in the CT and larger for CD8+ T 
      cells than for CD3+ T cells. The Immune-score integrating results from CT and IM 
      was also lower in transplant recipients. Density of TLS was lower in cancer 
      samples of transplant recipients. The fraction of samples with PD-L1 expression 
      was higher in controls whereas decreased expression of HLA-I was more common in 
      transplant recipients. CONCLUSIONS: Our study demonstrates the impact of 
      immunosuppression on the TME and supports impaired cancer immunosurveillance as 
      important cause of post-transplant cancer. Modern immunosuppressive protocols and 
      cancer therapies should consider the distinct immune microenvironment of 
      post-transplant malignancies.
CI  - (c)2022 American Association for Cancer Research.
FAU - Datta, Rabi R
AU  - Datta RR
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
FAU - Schran, Simon
AU  - Schran S
AUID- ORCID: 0000-0002-1092-9804
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
FAU - Persa, Oana-Diana
AU  - Persa OD
AUID- ORCID: 0000-0003-1469-4464
AD  - Department of Dermatology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
FAU - Aguilar, Claire
AU  - Aguilar C
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
FAU - Thelen, Martin
AU  - Thelen M
AUID- ORCID: 0000-0002-2785-9726
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
FAU - Lehmann, Jonas
AU  - Lehmann J
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
FAU - Garcia-Marquez, Maria A
AU  - Garcia-Marquez MA
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
FAU - Wennhold, Kerstin
AU  - Wennhold K
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
FAU - Preugszat, Ella
AU  - Preugszat E
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
FAU - Zentis, Peter
AU  - Zentis P
AUID- ORCID: 0000-0002-6999-132X
AD  - Cluster of Excellence for Aging-Associated Diseases, CECAD Imaging Facility 
      Cologne, University of Cologne, Cologne, Germany.
FAU - von Bergwelt-Baildon, Michael S
AU  - von Bergwelt-Baildon MS
AD  - Department of Internal Medicine III, University Hospital, Ludwig Maximilians 
      University, Munich, Germany.
FAU - Quaas, Alexander
AU  - Quaas A
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
AD  - Institute of Pathology, Faculty of Medicine and University Hospital Cologne, 
      University of Cologne, Cologne, Germany.
FAU - Bruns, Christiane J
AU  - Bruns CJ
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
FAU - Kurschat, Christine
AU  - Kurschat C
AUID- ORCID: 0000-0002-3646-9471
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
AD  - Department of Internal Medicine II, Faculty of Medicine and University Hospital 
      Cologne, University of Cologne, Cologne, Germany.
FAU - Mauch, Cornelia
AU  - Mauch C
AD  - Department of Dermatology, University of Cologne, Faculty of Medicine and 
      University Hospital Cologne, Cologne, Germany.
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
FAU - Loser, Heike
AU  - Loser H
AUID- ORCID: 0000-0003-4555-1327
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
AD  - Institute of Pathology, Faculty of Medicine and University Hospital Cologne, 
      University of Cologne, Cologne, Germany.
FAU - Stippel, Dirk L
AU  - Stippel DL
AUID- ORCID: 0000-0002-1107-0907
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
FAU - Schlosser, Hans A
AU  - Schlosser HA
AUID- ORCID: 0000-0002-1304-7719
AD  - Center for Molecular Medicine Cologne, Faculty of Medicine and University 
      Hospital Cologne, University of Cologne, Cologne, Germany.
AD  - Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of 
      Medicine and University Hospital Cologne, University of Cologne, Cologne, 
      Germany.
AD  - Center for Integrated Oncology, CIO ABCD Aachen, Bonn, Cologne, Dusseldorf.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - B7-H1 Antigen
MH  - Histocompatibility Antigens Class I
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating
MH  - Monitoring, Immunologic
MH  - *Neoplasms/etiology/metabolism
MH  - *Tertiary Lymphoid Structures
MH  - Tumor Microenvironment
EDAT- 2022/02/23 06:00
MHDA- 2022/04/16 06:00
CRDT- 2022/02/22 08:41
PHST- 2021/10/20 00:00 [received]
PHST- 2021/12/11 00:00 [revised]
PHST- 2022/02/03 00:00 [accepted]
PHST- 2022/02/23 06:00 [pubmed]
PHST- 2022/04/16 06:00 [medline]
PHST- 2022/02/22 08:41 [entrez]
AID - 681716 [pii]
AID - 10.1158/1078-0432.CCR-21-3746 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2022 Apr 14;28(8):1712-1723. doi: 10.1158/1078-0432.CCR-21-3746.