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e-Poster Display Session

100P - Patient-derived tissue cultures of esophagogastric-junction cancer (EGJC) and gastric cancer (GC): An ex vivo model to study individual response of immunotherapy

Date

09 Dec 2020

Session

e-Poster Display Session

Presenters

Justus Körfer

Citation

Annals of Oncology (2020) 31 (suppl_7): S1457-S1458. 10.1016/annonc/annonc394

Authors

J. Körfer1, M. Hußtegge1, I. Gockel1, A. Monecke1, G. Schumacher2

Author affiliations

  • 1 University Medicine Leipzig, Leipzig/DE
  • 2 Hospital Braunschweig, Braunschweig/DE
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Abstract 100P

Background

Novel oncological treatments targeting the immune system advance individual treatment strategies and prognosis. Robust predictive biomarkers and ex vivo models for patient stratification in EGJC/GC are still lacking. The model of patient-derived tissue cultures (PDTC) of EGJC/GC maintains the different cellular components of the natural cancer environment and is suitable to test tissue susceptibilities. Here, we analyse the preservation of T cells and their functionality in patient-derived tissue ex vivo.

Methods

PDTC were prepared from fresh surgical EGJC/GC specimens (n=15) and cultured over four days. To analyse T cell functionality tissues were treated with Nivolumab (Nivo) as single treatment and in combination with Oxaliplatin (Ox) or a CD3/CD28 T cell activator (Ic). Tissue morphology, proliferation and apoptosis of tumor cells were investigated by HE and immunofluorescence staining (panCK, Ki67, cPARP). T cells were characterized by immunohistochemistry (CD3, CD8, FoxP3).

Results

PDTC preserve the individual T cell populations in tissue cultures ex vivo. Patient specific response to single Nivo treatment ex vivo was observed. This result was not dependent on the amount of CD3 positive lymphocytes present in the individual tissue. Pooling all samples, application of Nivo combined with Ox or Ic enhanced the apoptosis rate compared to the untreated control. Investigating individual responses, the combination of Nivo and Ox showed enhanced tumor apoptosis compared to single drug treatment.

Conclusions

PDTC of EGJC/GC maintain their immunological tissue properties ex vivo, retaining T lymphocytes for four days in culture and demonstrating individual response to immune-stimulating drug application. The combined application of chemotherapy or overall T-cell activation with Nivo enhanced the overall tumor apoptosis, demonstrating potential beneficial effects of combinational therapy regimens. The maintenance of the individual immunological properties within the tissue specimens demonstrate the potential of the PDTC model for further investigating its relevance for clinical patient stratification.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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