PD-1 inhibition in patient derived tissue cultures of human gastric and gastroesophageal adenocarcinoma.
Marlon HußteggeNgoc Anh HoangJakob RebstockAstrid MoneckeInes GockelArved WeimannGuido SchumacherIngo BechmannFlorian LordickSonja KallendruschJustus KörferPublished in: Oncoimmunology (2021)
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.
Keyphrases
- endothelial cells
- gene expression
- peripheral blood
- immune response
- squamous cell carcinoma
- electronic health record
- dna methylation
- induced pluripotent stem cells
- locally advanced
- randomized controlled trial
- single cell
- signaling pathway
- big data
- case report
- mesenchymal stem cells
- risk assessment
- high intensity
- quality improvement
- patient safety
- combination therapy
- rectal cancer
- artificial intelligence
- deep learning