PMID- 35597867
OWN - NLM
STAT- MEDLINE
DCOM- 20220818
LR  - 20221113
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 127
IP  - 4
DP  - 2022 Sep
TI  - Modelling immune cytotoxicity for cholangiocarcinoma with tumour-derived 
      organoids and effector T cells.
PG  - 649-660
LID - 10.1038/s41416-022-01839-x [doi]
AB  - BACKGROUND: Immunotherapy with immune checkpoint inhibitors (ICIs) is being 
      explored to improve cholangiocarcinoma (CCA) therapy. However, it remains 
      difficult to predict which ICI will be effective for individual patients. 
      Therefore, the aim of this study is to develop a co-culture method with 
      patient-derived CCA organoids and immune cells, which could represent anti-cancer 
      immunity in vitro. METHODS: CCA organoids were co-cultured with peripheral blood 
      mononuclear cells or T cells. Flow cytometry, time-lapse confocal imaging for 
      apoptosis, and quantification of cytokeratin 19 fragment (CYFRA) release were 
      applied to analyse organoid and immune cell behaviour. CCA organoids were also 
      cultured in immune cell-conditioned media to analyse the effect of soluble 
      factors. RESULTS: The co-culture system demonstrated an effective anti-tumour 
      organoid immune response by a decrease in live organoid cells and an increase in 
      apoptosis and CYFRA release. Interpatient heterogeneity was observed. The 
      cytotoxic effects could be mediated by direct cell-cell contact and by release of 
      soluble factors, although soluble factors only decreased viability in one 
      organoid line. CONCLUSIONS: In this proof-of-concept study, a novel CCA organoid 
      and immune cell co-culture method was established. This can be the first step 
      towards personalised immunotherapy for CCA by predicting which ICIs are most 
      effective for individual patients.
CI  - (c) 2022. The Author(s).
FAU - Zhou, Guoying
AU  - Zhou G
AUID- ORCID: 0000-0002-0108-2103
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands. estelly88@gmail.com.
FAU - Lieshout, Ruby
AU  - Lieshout R
AUID- ORCID: 0000-0002-7848-3933
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - van Tienderen, Gilles S
AU  - van Tienderen GS
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - de Ruiter, Valeska
AU  - de Ruiter V
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - van Royen, Martin E
AU  - van Royen ME
AUID- ORCID: 0000-0002-6814-0996
AD  - Department of Pathology, Erasmus MC University Medical Center Rotterdam, 
      Rotterdam, The Netherlands.
FAU - Boor, Patrick P C
AU  - Boor PPC
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - Magre, Luc
AU  - Magre L
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - Desai, Jyaysi
AU  - Desai J
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - Koten, Kubra
AU  - Koten K
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - Kan, Yik Yang
AU  - Kan YY
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - Ge, Zhouhong
AU  - Ge Z
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - Campos Carrascosa, Lucia
AU  - Campos Carrascosa L
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - Geuijen, Cecile
AU  - Geuijen C
AD  - Merus N.V., Utrecht, The Netherlands.
FAU - Sprengers, Dave
AU  - Sprengers D
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
FAU - van der Laan, Luc J W
AU  - van der Laan LJW
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands.
FAU - Verstegen, Monique M A
AU  - Verstegen MMA
AUID- ORCID: 0000-0001-9908-6673
AD  - Department of Surgery, Erasmus MC Transplant Institute, Erasmus MC University 
      Medical Center Rotterdam, Rotterdam, The Netherlands. m.verstegen@erasmusmc.nl.
FAU - Kwekkeboom, Jaap
AU  - Kwekkeboom J
AD  - Department of Gastroenterology and Hepatology, Erasmus MC University Medical 
      Center Rotterdam, Rotterdam, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220521
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
SB  - IM
MH  - *Bile Duct Neoplasms
MH  - Bile Ducts, Intrahepatic/pathology
MH  - *Cholangiocarcinoma
MH  - Humans
MH  - Leukocytes, Mononuclear/metabolism
MH  - Organoids
MH  - T-Lymphocytes/pathology
PMC - PMC9381772
COIS- The authors declare no competing interests.
EDAT- 2022/05/22 06:00
MHDA- 2022/08/19 06:00
PMCR- 2022/05/21
CRDT- 2022/05/21 23:19
PHST- 2021/11/02 00:00 [received]
PHST- 2022/04/28 00:00 [accepted]
PHST- 2022/04/15 00:00 [revised]
PHST- 2022/05/22 06:00 [pubmed]
PHST- 2022/08/19 06:00 [medline]
PHST- 2022/05/21 23:19 [entrez]
PHST- 2022/05/21 00:00 [pmc-release]
AID - 10.1038/s41416-022-01839-x [pii]
AID - 1839 [pii]
AID - 10.1038/s41416-022-01839-x [doi]
PST - ppublish
SO  - Br J Cancer. 2022 Sep;127(4):649-660. doi: 10.1038/s41416-022-01839-x. Epub 2022 
      May 21.