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FIGURE 3 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 reduces PDAC progression. A, Tumor volume and weight in WT and Nlrp3−/− mice (n = 8/group). B, Tumor volume and weight in mice fed standard (STD) or OL1177 (OLT) diet (n = 16/group). C, Survival curve in mice fed standard or OLT1177 diet (n = 20/group). D, Flow cytometry analysis of CD8, CD8/PD1, CD8/CD44/PD-1 cells in primary tumors of mice in B (n = 5/group). E, Flow cytometry analysis of memory (CD62L+/CD44+), naïve (CD62L+/CD44), and effector (CD62L/CD44+) CD8 cells in primary tumors of mice in D–F (n = 5/group). F, Gene expression of Ifng, Prf1, and Gzmb in primary tumors of mice in B (n = 5/group). Data expressed as mean ± SEM; ****, P < 0.0001; **, 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.