PMID- 34434611 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20220531 IS - 2162-402X (Electronic) IS - 2162-4011 (Print) IS - 2162-4011 (Linking) VI - 10 IP - 1 DP - 2021 TI - PD-1 inhibition in patient derived tissue cultures of human gastric and gastroesophageal adenocarcinoma. PG - 1960729 LID - 10.1080/2162402X.2021.1960729 [doi] LID - 1960729 AB - 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 ImmunoCult(TM). 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 ImmunoCult(TM). 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. CI - (c) 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. FAU - Husstegge, Marlon AU - Husstegge M AD - Institute of Anatomy, University of Leipzig, Leipzig. AD - Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. FAU - Hoang, Ngoc Anh AU - Hoang NA AD - Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. FAU - Rebstock, Jakob AU - Rebstock J AD - Institute of Anatomy, University of Leipzig, Leipzig. AD - Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. FAU - Monecke, Astrid AU - Monecke A AD - Institute of Pathology, University Hospital Leipzig, Leipzig, Germany. FAU - Gockel, Ines AU - Gockel I AD - Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. FAU - Weimann, Arved AU - Weimann A AD - Department for General and Visceral Surgery, Hospital St. Georg Leipzig, Leipzig, Germany. FAU - Schumacher, Guido AU - Schumacher G AD - Department for General and Visceral Surgery, Hospital Braunschweig, Braunschweig, Germany. FAU - Bechmann, Ingo AU - Bechmann I AD - Institute of Anatomy, University of Leipzig, Leipzig. FAU - Lordick, Florian AU - Lordick F AD - Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. FAU - Kallendrusch, Sonja AU - Kallendrusch S AUID- ORCID: 0000-0003-2474-8307 AD - Institute of Anatomy, University of Leipzig, Leipzig. FAU - Korfer, Justus AU - Korfer J AD - Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210818 PL - United States TA - Oncoimmunology JT - Oncoimmunology JID - 101570526 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Programmed Cell Death 1 Receptor) RN - 31YO63LBSN (Nivolumab) SB - IM MH - Adenocarcinoma/*drug therapy MH - Esophageal Neoplasms/*drug therapy MH - *Esophagogastric Junction MH - Humans MH - Immune Checkpoint Inhibitors/pharmacology/*therapeutic use MH - Leukocytes, Mononuclear MH - Nivolumab/pharmacology/*therapeutic use MH - Programmed Cell Death 1 Receptor/*antagonists & inhibitors PMC - PMC8381835 OTO - NOTNLM OT - Gastric cancer OT - immune response to cancer OT - immunology OT - immunotherapy OT - patient derived tissue culture COIS- The authors declare no potential conflicts of interest. EDAT- 2021/08/27 06:00 MHDA- 2021/10/16 06:00 PMCR- 2021/08/18 CRDT- 2021/08/26 06:15 PHST- 2021/08/26 06:15 [entrez] PHST- 2021/08/27 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2021/08/18 00:00 [pmc-release] AID - 1960729 [pii] AID - 10.1080/2162402X.2021.1960729 [doi] PST - epublish SO - Oncoimmunology. 2021 Aug 18;10(1):1960729. doi: 10.1080/2162402X.2021.1960729. eCollection 2021.