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Updated: Oct 12, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma
Darci Phillips1,2,3, Magdalena Matusiak3, Belén Rivero Gutierrez3
1Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Abstract:
Cutaneous T cell lymphomas (CTCL) are rare but aggressive cancers without effective treatments. While a subset of patients derive benefit from PD-1 blockade, there is a critically unmet need for predictive biomarkers of response. Herein, we perform CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced CTCL patients enrolled in a pembrolizumab clinical trial (NCT02243579). We find no differences in the frequencies of immune or tumor cells between responders and non-responders. Instead, we identify topographical differences between effector PD-1+ CD4+ T cells, tumor cells, and immunosuppressive Tregs, from which we derive a spatial biomarker, termed the SpatialScore, that correlates strongly with pembrolizumab response in CTCL. The SpatialScore coincides with differences in the functional immune state of the tumor microenvironment, T cell function, and tumor cell-specific chemokine recruitment and is validated using a simplified, clinically accessible tissue imaging platform. Collectively, these results provide a paradigm for investigating the spatial balance of effector and suppressive T cell activity and broadly leveraging this biomarker approach to inform the clinical use of immunotherapies.
Insights
A new spatial biomarker, SpatialScore, predicts response to PD-1 blockade immunotherapy in cutaneous T cell lymphomas (CTCL). This finding offers a novel approach for guiding CTCL treatment decisions.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Cutaneous T cell lymphomas (CTCL) are aggressive cancers with limited effective treatments.
- PD-1 blockade shows efficacy in a subset of CTCL patients, highlighting the need for predictive biomarkers.
- Current biomarkers do not adequately predict response to immunotherapy in CTCL.
Purpose of the Study:
- To identify predictive biomarkers for PD-1 blockade response in advanced CTCL.
- To investigate the spatial relationships of immune and tumor cells in the tumor microenvironment.
- To develop a novel spatial biomarker for guiding immunotherapy decisions in CTCL.
Main Methods:
- CODEX multiplexed tissue imaging and RNA sequencing were performed on tumor samples from 14 advanced CTCL patients in a pembrolizumab clinical trial.
- Analysis focused on immune cell populations, tumor cells, and their spatial organization.
- A spatial biomarker, SpatialScore, was derived based on topographical differences between specific cell types.
Main Results:
- No significant differences in immune or tumor cell frequencies were observed between responders and non-responders.
- Topographical differences in the spatial distribution of effector PD-1+ CD4+ T cells, tumor cells, and Tregs were identified.
- The derived SpatialScore strongly correlated with pembrolizumab response and reflected functional immune states and chemokine recruitment.
- The SpatialScore was validated using a simplified, clinically accessible tissue imaging platform.
Conclusions:
- Spatial organization of immune cells, not just their frequency, is critical for predicting immunotherapy response in CTCL.
- The SpatialScore serves as a promising predictive biomarker for PD-1 blockade in CTCL.
- This spatial biomarker approach offers a new paradigm for optimizing immunotherapy use in cancer treatment.
