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

Marlon Hußtegge; Ngoc Anh Hoang; Jakob Rebstock; Astrid Monecke; Ines Gockel; Arved Weimann; Guido Schumacher; Ingo Bechmann; Florian Lordick; Sonja Kallendrusch; Justus Körfer

doi:10.1080/2162402X.2021.1960729

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

Oncoimmunology. 2021 Aug 18;10(1):1960729. doi: 10.1080/2162402X.2021.1960729. eCollection 2021.

Authors

Affiliations

¹ Institute of Anatomy, University of Leipzig, Leipzig.
² Department of Oncology, Gastroenterology, Hepatology, Pulmonology, and Infectious Diseases, University Cancer Center Leipzig, University Hospital Leipzig, Leipzig, Germany.
³ Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.
⁴ Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
⁵ Department for General and Visceral Surgery, Hospital St. Georg Leipzig, Leipzig, Germany.
⁶ Department for General and Visceral Surgery, Hospital Braunschweig, Braunschweig, Germany.

Abstract

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.

Keywords: Gastric cancer; immune response to cancer; immunology; immunotherapy; patient derived tissue culture.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / drug therapy*
Esophageal Neoplasms / drug therapy*
Esophagogastric Junction*
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use*
Leukocytes, Mononuclear
Nivolumab / pharmacology
Nivolumab / therapeutic use*
Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

Immune Checkpoint Inhibitors
Programmed Cell Death 1 Receptor
Nivolumab

Grants and funding

The project was sponsored by the Junior research grant of the Medical Faculty, University of Leipzig;