American Association for Cancer Research
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FIGURE 8 from Pancreatic Ductal Adenocarcinoma Cells Regulate NLRP3 Activation to Generate a Tolerogenic Microenvironment

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posted on 2023-09-20, 14:20 authored by Jesus Amo-Aparicio, Adrian Dominguez, Shaikh M. Atif, Alberto Dinarello, Tania Azam, Kibrom M. Alula, Miles Piper, Christopher H. Lieu, Robert W. Lentz, Alexis D. Leal, Stacey M. Bagby, Wells A. Messersmith, Sana D. Karam, Charles A. Dinarello, Todd M. Pitts, Carlo Marchetti

NLRP3 inhibition increases gemcitabine efficacy. A, Tumor volume and weight in mice treated with vehicle (PBS), gemcitabine (GEM), OLT1177 (OLT), and GEM+OLT (n = 8/group). B, Flow cytometry analysis of Ki67 expression in CD45 cells from the primary tumors obtained in A (n = 8/group). C, Viability of human PDAC organoids after 72 hours of culture in presence of gemcitabine (GEM) or OLT1177 (OLT; n = 3). D, Representative images of organoids from C. E, NLRP3 expression in primary tumors obtained in A (n = 3/group). Data expressed as mean ± SEM; ****, P < 0.0001; ***, P < 0.001; **, P < 0.01; *, P < 0.05.

Funding

Wings of hope for pancreatic cancer research

American Cancer Society (ACS)

CU | Cancer Center, University of Colorado (CU Cancer Center)

Amini Pancreatic Cancer Research Fund

HHS | NIH | National Cancer Institute (NCI)

Gina Guy Chair in Pancreatic Cancer Research

HHS | National Institutes of Health (NIH)

History

ARTICLE ABSTRACT

This study provides novel molecular insights on how PDAC cells exploit NLRP3 activation to suppress CD8 T-cell activation. From a translational perspective, we demonstrate that the combination of gemcitabine with the orally active NLRP3 inhibitor OLT1177 increases the efficacy of monotherapy.