PMID- 34309588
OWN - NLM
STAT- MEDLINE
DCOM- 20211015
LR  - 20211015
IS  - 1940-087X (Electronic)
IS  - 1940-087X (Linking)
IP  - 173
DP  - 2021 Jul 6
TI  - A Preclinical Human-Derived Autologous Gastric Cancer Organoid/Immune Cell 
      Co-Culture Model to Predict the Efficacy of Targeted Therapies.
LID - 10.3791/61443 [doi]
AB  - Tumors expressing programmed cell death-ligand 1 (PD-L1) interact with programmed 
      cell death protein 1 (PD-1) on CD8+ cytotoxic T lymphocytes (CTLs) to evade 
      immune surveillance leading to the inhibition of CTL proliferation, survival, and 
      effector function, and subsequently cancer persistence. Approximately 40% of 
      gastric cancers express PD-L1, yet the response rate to immunotherapy is only 
      30%. We present the use of human-derived autologous gastric cancer 
      organoid/immune cell co-culture as a preclinical model that may predict the 
      efficacy of targeted therapies to improve the outcome of cancer patients. 
      Although cancer organoid co-cultures with immune cells have been reported, this 
      co-culture approach uses tumor antigen to pulse the antigen-presenting dendritic 
      cells. Dendritic cells (DCs) are then cultured with the patient's CD8+ T cells to 
      expand the cytolytic activity and proliferation of these T lymphocytes before 
      co-culture. In addition, the differentiation and immunosuppressive function of 
      myeloid-derived suppressor cells (MDSCs) in culture are investigated within this 
      co-culture system. This organoid approach may be of broad interest and 
      appropriate to predict the efficacy of therapy and patient outcome in other 
      cancers, including pancreatic cancer.
FAU - Chakrabarti, Jayati
AU  - Chakrabarti J
AD  - Department of Cellular and Molecular Medicine, University of Arizona, Tucson.
FAU - Koh, Vivien
AU  - Koh V
AD  - National University Cancer Institute Singapore, National University Health 
      System, Singapore; Cancer Science Institute of Singapore, National University of 
      Singapore.
FAU - So, Jimmy Bok Yan
AU  - So JBY
AD  - National University Cancer Institute Singapore, National University Health 
      System, Singapore; Department of Surgery, Yong Loo Lin School of Medicine, 
      National University of Singapore.
FAU - Yong, Wei Peng
AU  - Yong WP
AD  - National University Cancer Institute Singapore, National University Health 
      System, Singapore; Cancer Science Institute of Singapore, National University of 
      Singapore; wei_peng_yong@nuhs.edu.sg.
FAU - Zavros, Yana
AU  - Zavros Y
AD  - Department of Cellular and Molecular Medicine, University of Arizona, Tucson; 
      yzavros@arizona.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Video-Audio Media
DEP - 20210706
PL  - United States
TA  - J Vis Exp
JT  - Journal of visualized experiments : JoVE
JID - 101313252
RN  - 0 (B7-H1 Antigen)
SB  - IM
MH  - B7-H1 Antigen
MH  - Coculture Techniques
MH  - Humans
MH  - Organoids
MH  - *Stomach Neoplasms/therapy
MH  - T-Lymphocytes, Cytotoxic
EDAT- 2021/07/27 06:00
MHDA- 2021/10/16 06:00
CRDT- 2021/07/26 12:25
PHST- 2021/07/26 12:25 [entrez]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/10/16 06:00 [medline]
AID - 10.3791/61443 [doi]
PST - epublish
SO  - J Vis Exp. 2021 Jul 6;(173). doi: 10.3791/61443.