Abstract

<div>Abstract<p><b>Purpose:</b> Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate <7% and is ultimately refractory to most treatments. To date, an assessment of immunologic factors relevant to disease has not been comprehensively performed for treatment-naïve patients. We hypothesized that systemic immunologic biomarkers could predict overall survival (OS) in treatment-naïve PDAC patients.</p><p><b>Experimental Design:</b> Peripheral blood was collected from 73 patients presenting with previously untreated metastatic PDAC. Extensive immunologic profiling was conducted to assess relationships between OS and the level of soluble plasma biomarkers or detailed immune cell phenotypes as measured by flow cytometry.</p><p><b>Results:</b> Higher baseline levels of the immunosuppressive cytokines IL6 and IL10 were strongly associated with poorer OS (<i>P</i> = 0.008 and 0.026, respectively; HR = 1.16 and 1.28, respectively), whereas higher levels of the monocyte chemoattractant MCP-1 were associated with significantly longer OS (<i>P</i> = 0.045; HR = 0.69). Patients with a greater proportion of antigen-experienced T cells (CD45RO<sup>+</sup>) had longer OS (CD4 <i>P</i> = 0.032; CD8 <i>P</i> = 0.036; HR = 0.36 and 0.61, respectively). Although greater expression of the T-cell checkpoint molecule CTLA-4 on CD8<sup>+</sup> T cells was associated with significantly shorter OS (<i>P</i> = 0.020; HR = 1.53), the TIM3 molecule had a positive association with survival when expressed on CD4<sup>+</sup> T cells (<i>P</i> = 0.046; HR = 0.62).</p><p><b>Conclusions:</b> These data support the hypothesis that baseline immune status predicts PDAC disease course and overall patient survival. To our knowledge, this work represents the largest cohort and most comprehensive immune profiling of treatment-naïve metastatic PDAC patients to date. <i>Clin Cancer Res; 22(10); 2565–74. ©2015 AACR</i>.</p></div>

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.