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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
14.9K
T cell subtype profiling measures exhaustion and predicts anti-PD-1 response
Ian Schillebeeckx1, Jon Earls2, Kevin C Flanagan2
1Cofactor Genomics, Inc., San Francisco, CA, USA. ian@cofactorgenomics.com.
Scientific Reports
|January 26, 2022
Summary
T Cell Subtype Profiling (TCSP) offers a novel biomarker for predicting anti-PD-1 therapy response. This method accurately identifies T cell subtypes, outperforming current PD-L1 tests and Tumor Mutational Burden in predicting patient outcomes.
Area of Science:
- Immunology
- Biomarker Discovery
- Cancer Research
Background:
- Anti-PD-1 therapy offers durable benefits but response prediction remains challenging.
- Current PD-L1 testing lacks sufficient accuracy for predicting treatment efficacy.
- Need for improved biomarkers to guide anti-PD-1 therapy selection.
Purpose of the Study:
- To develop and validate a novel biomarker for predicting anti-PD-1 therapy response.
- To characterize T cell subtypes (TCSs) in FFPE specimens using RNA models.
- To create a resource for discovering new TCSP-based biomarkers.
Main Methods:
- Developed T Cell Subtype Profiling (TCSP) using five RNA models.
- TCSP characterizes naïve, activated, exhausted, effector memory, and central memory TCSs.
- Validated TCSP's analytical validity and clinical outcome associations.
Main Results:
- TCSP accurately discriminates between distinct T cell subtypes.
- Multianalyte biomarkers based on TCSP predicted anti-PD-1 response in three cancers.
- TCSP-based biomarkers outperformed PD-L1 tests and Tumor Mutational Burden.
Conclusions:
- TCSP is a robust and accurate method for T cell subtype characterization.
- TCSP-based biomarkers demonstrate superior predictive value for anti-PD-1 therapy.
- A portal was created to facilitate further research and biomarker discovery using TCSP.

