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PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

Davern, Maria
Gaughan, Caoimhe
O' Connell, Fiona
Moran, Brendan
Mylod, Eimear
Sheppard, Andrew D
Ramjit, Sinead
Yun-Tong Kung, Jasmine
Phelan, James J
Davey, Matthew G
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Date
2023-06-09
Date Submitted
Keywords
PD-1
TIGIT
Th1 immunity
Immunosuppression
nivolumab and ipilimumab
oesophageal adenocarcinoma
Perioperative
surgery
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Abstract
PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity.
Language
en
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1664-3224
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DOI
10.3389/fimmu.2023.1150754
PMID
37359545
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