TY - JOUR
T1 - Pembrolizumab followed by irreversible electroporation of a liver metastasis in pancreatic cancer patients
AU - Flak, Rasmus Virenfeldt
AU - Kofod-Olsen, Emil
AU - Sølvsten, Nikolaj Dich
AU - Naujokaite, Gintare
AU - Agger, Ralf
AU - Stender, Mogens Tornby
AU - Christensen, Signe
AU - Shim, Susy
AU - Poulsen, Laurids Østergaard
AU - Detlefsen, Sönke
AU - Thorlasius-Ussing, Ole
AU - Ladekarl, Morten
N1 - © 2024 The Author(s).
PY - 2024/10/18
Y1 - 2024/10/18
N2 - Preclinical studies suggest that irreversible electroporation (IRE) increases the effect of immune checkpoint inhibition in pancreatic cancer (PC). Patients with PC received PD-1 inhibitor pembrolizumab and, on day 10, percutaneous IRE of a liver metastasis. Blood samples were analyzed for immune cell subsets and inflammation related proteins. mRNA expression profiling was done in sequential biopsies. Treatment was safe, but the trial was terminated early. The response rate in eight patients was 0% and tumor growth was exponential. A drop in circulating plasmacytoid dendritic cells and a rise in several cytokines and proteins, especially PD-1, after immunotherapy was observed. In liver metastases, immune stimulatory genes were upregulated and immune suppressive genes were downregulated after pembrolizumab, while markers of effector T cells were unchanged. Treatment was safe but showed no efficacy in PC. Immunotherapy induced an immune permissive tumor microenvironment but with no increase in effector cells.
AB - Preclinical studies suggest that irreversible electroporation (IRE) increases the effect of immune checkpoint inhibition in pancreatic cancer (PC). Patients with PC received PD-1 inhibitor pembrolizumab and, on day 10, percutaneous IRE of a liver metastasis. Blood samples were analyzed for immune cell subsets and inflammation related proteins. mRNA expression profiling was done in sequential biopsies. Treatment was safe, but the trial was terminated early. The response rate in eight patients was 0% and tumor growth was exponential. A drop in circulating plasmacytoid dendritic cells and a rise in several cytokines and proteins, especially PD-1, after immunotherapy was observed. In liver metastases, immune stimulatory genes were upregulated and immune suppressive genes were downregulated after pembrolizumab, while markers of effector T cells were unchanged. Treatment was safe but showed no efficacy in PC. Immunotherapy induced an immune permissive tumor microenvironment but with no increase in effector cells.
KW - clinical finding
KW - clinical stage
KW - Health sciences
KW - oncology
UR - http://www.scopus.com/inward/record.url?scp=85207328944&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.111026
DO - 10.1016/j.isci.2024.111026
M3 - Journal article
C2 - 39610376
AN - SCOPUS:85207328944
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 10
M1 - 111026
ER -