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. We performed CODEX multiplexed tissue imaging on 70 tumor regions from 14 advanced CTCL patients enrolled in a pembrolizumab clinical trial. We found no differences in the frequencies of immune or tumor cells between responders and non-responders. Instead, we identified topographical differences between effector PD-1+ CD4+ T cells, tumor cells, and immunosuppressive Tregs, from which we derived a spatial biomarker, termed the SpatialScore, that correlated strongly with pembrolizumab response. 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.