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9.fastq.gzprimaryOK200Genomicsvan de Rijn West lab, Pathology, Stanford Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA680750Homo sapiensxref:PubMed:34795254Anti-PD-1 immunotherapies have transformed cancer treatment, but the determinants of clinical response are largely unknown. We performed CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions of advanced cutaneous T cell lymphoma (CTCL) from 14 patients enrolled in a clinical trial of pembrolizumab therapy. Clinical response was not associated with the frequency of tumor-infiltrating T cell subsets, but rather with striking differences in the spatial organization and functional immune state of the tumor microenvironment (TME). After treatment, pembrolizumab responders had a localized enrichment of tumor and CD4+ T cells, which coincided with immune activation and cytotoxic PD-1+ CD4+ T cells. In contrast, non-responders had a localized enrichment of Tregs pre- and post-treatment, consistent with a persistently immunosuppressed TME and exhausted PD-1+ CD4+ T cells. Integrating these findings by computing the physical distances between PD-1+ CD4+ T cells, tumor cells, and Tregs revealed a spatial biomarker predictive of pembrolizumab response. Finally, the chemokine CXCL13 was upregulated in tumor cells in responders post-treatment, suggesting that chemoattraction of PD-1+ CD4+ T cells towards tumor cells facilitates a positive outcome. Together, these data show that T cell topography reflects the balance of effector and suppressive activity within the TME and predicts clinical response to PD-1 blockade in CTCL. Overall design: We Laser Capture Microdisected regions containing approximately 1000 cells from FFPE-tissue of CTCL lesions from responders and non responders before and after treatment with pembrolizumab.ENACTCL, cutaneous T-cell lymphoma, immune cell, SLEB2, T-cell non-Hodgkin's lymphoma of skin, l17, Cutaneous T-Cell Lymphoma, PMN cell, primary cutaneous T-cell non-Hodgkin lymphoma, Granulomatous Slack Skin, Cutaneous T-Cell, RPL23, rpl17a, pd-1, T-cell non-Hodgkin's lymphoma of the skin, Cutaneous T Cell Lymphoma, Lymphomas, PD1, PD-1, Ly101, leucocyte, Slack Skin, cutaneous T cell lymphoma, skin T-cell non-Hodgkin's lymphoma, 60S ribosomal protein L23, rpl23, cutaneous T-cell non-Hodgkin's lymphoma, PMNC, T Cell Lymphoma, CD279, hPD-1, Cutaneous T-Cell., Granulomatous, cutaneous T-cell non-Hodgkin lymphoma, primary cutaneous T-cell non-Hodgkin's lymphoma, white blood cell, hPD-l, Pdc1, Cutaneous T-Cell Lymphomas, hSLE1, Lymphoma, PCTCL, rpl17, L17, T Cell, T-Cell Lymphoma, T-Cell Lymphomas, polymorphonuclear cell, CutaneousCTCL, cutaneous T-cell lymphoma, immune cell, SLEB2, T-cell non-Hodgkin's lymphoma of skin, l17, Cutaneous T-Cell Lymphoma, PMN cell, primary cutaneous T-cell non-Hodgkin lymphoma, Granulomatous Slack Skin, Cutaneous T-Cell, RPL23, rpl17a, pd-1, T-cell non-Hodgkin's lymphoma of the skin, Cutaneous T Cell Lymphoma, Lymphomas, PD1, PD-1, Ly101, leucocyte, Slack Skin, cutaneous T cell lymphoma, skin T-cell non-Hodgkin's lymphoma, 60S ribosomal protein L23, rpl23, cutaneous T-cell non-Hodgkin's lymphoma, PMNC, T Cell Lymphoma, CD279, hPD-1, Cutaneous T-Cell., Granulomatous, cutaneous T-cell non-Hodgkin lymphoma, primary cutaneous T-cell non-Hodgkin's lymphoma, white blood cell, hPD-l, Pdc1, Cutaneous T-Cell Lymphomas, hSLE1, Lymphoma, PCTCL, rpl17, L17, T Cell, T-Cell Lymphoma, T-Cell Lymphomas, polymorphonuclear cell, CutaneousfalseImmune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphomaImmune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma2025-09-242021-09-20PRJNA680750GSE162137960634795254