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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
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Methylation-Based ctDNA Tumor Fraction Changes Predict Long-Term Clinical Benefit From Immune Checkpoint Inhibitors

Samantha I Liang1, Zoe Quandt2, Sara Wienke3

  • 1Parker Institute for Cancer Immunotherapy, San Francisco, California.

Cancer Research Communications
|July 29, 2025
PubMed
Summary
This summary is machine-generated.

Monitoring circulating tumor DNA (ctDNA) methylation-based tumor fraction (TF) can accurately assess tumor burden and predict outcomes in patients receiving immune checkpoint inhibition (ICI). Early decreases in TF indicate superior survival, supporting its use in real-world cancer care.

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Cancer Genomics

Background:

  • Current cancer response evaluation methods have limitations in accuracy.
  • Circulating tumor DNA (ctDNA) methylation-based tumor fraction (TF) offers a potential method for assessing tumor burden in solid tumors.
  • Immune checkpoint inhibition (ICI) is a standard treatment for many advanced cancers.

Purpose of the Study:

  • To evaluate a tissue-free, methylation-based ctDNA TF assay for monitoring tumor burden.
  • To explore the association between methylation-based TF and treatment outcomes in patients receiving ICI.
  • To assess the lead time of nonmolecular response (nMR) detection prior to clinical progression.

Main Methods:

  • Analysis of 1,997 plasma samples from 627 patients with stage IV cancer receiving ICI in the RADIOHEAD cohort.
  • Utilized a validated next-generation sequencing methylation-based ctDNA assay (Guardant Reveal).
  • Primary outcome: real-world progression-free survival (rwPFS); Secondary outcomes: real-world overall survival (rwOS) and lead time to nMR.

Main Results:

  • Patients with any decrease in TF during ICI treatment showed superior outcomes.
  • A ≥80% decrease in TF or TF below limit of quantification correlated with longer rwPFS and rwOS.
  • Nonmolecular response (nMR) was detected a median of 3.03 months before clinical progression.

Conclusions:

  • Methylation-based TF monitoring in patients with stage IV cancer receiving ICI identifies those with significantly longer rwPFS and rwOS.
  • Changes in TF provide earlier response data than imaging alone.
  • Serial monitoring of TF has the potential to inform treatment decisions in real-world cancer care.