Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy.
Jelena LeviTina LamSamuel R GothShahriar YaghoubiJennifer BatesGang RenSalma JivanTony L HuynhJoseph E BlechaRoli KhattriKarl F SchmidtDominique JenningsHenry F VanBrocklinPublished in: Cancer research (2019)
Compelling evidence points to immune cell infiltration as a critical component of successful immunotherapy. However, there are currently no clinically available, noninvasive methods capable of evaluating immune contexture prior to or during immunotherapy. In this study, we evaluate a T-cell-specific PET agent, [18F]F-AraG, as an imaging biomarker predictive of response to checkpoint inhibitor therapy. We determined the specificity of the tracer for activated T cells in vitro and in a virally induced model of rhabdomyosarcoma. Of all immune cells tested, activated human CD8+ effector cells showed the highest accumulation of [18F]F-AraG. Isolation of lymphocytes from the rhabdomyosarcoma tumors showed that more than 80% of the intratumoral signal came from accumulation of [18F]F-AraG in immune cells, primarily CD8+ and CD4+. Longitudinal monitoring of MC38 tumor-bearing mice undergoing anti-PD-1 treatment revealed differences in signal between PD-1 and isotype antibody-treated mice early into treatment. The differences in [18F]F-AraG signal were also apparent between responders and nonresponders to anti-PD-1 therapy. Importantly, we found that the signal in the tumor-draining lymph nodes provides key information about response to anti-PD-1 therapy. Overall, [18F]F-AraG has potential to serve as a much needed immunomonitoring clinical tool for timely evaluation of immunotherapy. SIGNIFICANCE: These findings reveal differences in T-cell activation between responders and nonresponders early into anti-PD-1 treatment, which may impact many facets of immuno-oncology, including patient selection, management, and development of novel combinatorial approaches.
Keyphrases
- immune response
- lymph node
- high resolution
- healthcare
- dna damage
- endothelial cells
- metabolic syndrome
- magnetic resonance imaging
- palliative care
- type diabetes
- replacement therapy
- dna methylation
- social media
- combination therapy
- risk assessment
- dendritic cells
- mass spectrometry
- bone marrow
- signaling pathway
- adipose tissue
- insulin resistance
- pet ct
- fluorescence imaging
- climate change
- sentinel lymph node
- pet imaging