PD-1 inhibition in patient derived tissue cultures of human gastric and gastroesophageal adenocarcinoma

Autor: Marlon Hußtegge, Ngoc Anh Hoang, Jakob Rebstock, Astrid Monecke, Ines Gockel, Arved Weimann, Guido Schumacher, Ingo Bechmann, Florian Lordick, Sonja Kallendrusch, Justus Körfer
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: OncoImmunology, Vol 10, Iss 1 (2021)
Druh dokumentu: article
ISSN: 2162-402X
2162402X
DOI: 10.1080/2162402X.2021.1960729
Popis: Emerging immunotherapies quest for better patient stratification in cancer treatment decisions. Moderate response rates of PD-1 inhibition in gastric and esophagogastric junction cancers urge for meaningful human model systems that allow for investigating immune responses ex vivo. Here, the standardized patient-derived tissue culture (PDTC) model was applied to investigate tumor response to the PD-1 inhibitor Nivolumab and the CD3/CD28 t-lymphocyte activator ImmunoCultTM. Resident t-lymphocytes, tumor proliferation and apoptosis, as well as bulk gene expression data were analyzed after 72 h of PD-1 inhibition either as monotherapy or combined with Oxaliplatin or ImmunoCultTM. Individual responses to PD-1 inhibition were found ex vivo and combination with chemotherapy or t-lymphocyte activation led to enhanced antitumoral effects in PDTCs. T-lymphocyte activation as well as the addition of pre-cultured peripheral blood mononuclear cells improved PDTC for studying t-lymphocyte and tumor cell communication. These data support the potential of PDTC to investigate immunotherapy ex vivo in gastric and esophagogastric junction cancer.
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