{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:03:54Z","timestamp":1784624634585,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007313","name":"MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["2023-00062067"],"award-info":[{"award-number":["2023-00062067"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007313","name":"MD Anderson Cancer Center","doi-asserted-by":"publisher","award":["NIH P30CA16672"],"award-info":[{"award-number":["NIH P30CA16672"]}],"id":[{"id":"10.13039\/100007313","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fred Pearce Fund","award":["122209"],"award-info":[{"award-number":["122209"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Mycosis fungoides (MF) and S\u00e9zary syndrome (SS) are the predominant cutaneous T-cell lymphomas. Although malignant T cells in MF\/SS overexpress CCR4 and respond to the anti-CCR4 antibody mogamulizumab, skin response rates vary. We hypothesized that immune components within the tumor microenvironment contribute to differential outcomes. Methods: Imaging mass cytometry with a 37-antibody panel was used to characterize immune and structural elements in FFPE tissues from sixteen MF\/SS patients (6 MF, 10 SS) treated with Mogamulizumab, including seven skin responders and nine non-responders. Single-cell phenotyping and spatial analyses were performed using the Visiopharm\u00ae Phenoplex\u2122 platform, with supervision. Results: We identified 68,974 cells pre-treatment and 58,852 cells post-treatment. Malignant CD4+ T cells showed reduced baseline CD27, CD103, CD25, and ICOS expression compared with non-malignant CD4+ cells. Baseline MF lesions were enriched for IL-13+ and CD103+ malignant T cells, whereas SS lesions contained higher proportions of CD27+ and LAG3+ cells. IL 13+ malignant cells decreased after treatment, most prominently in MF. Myeloid profiles differed by disease and response: MF lesions exhibited baseline enrichment of M1-like macrophages (CD86+, HLA-DR+), while SS lesions were predominantly M2-polarized macrophages (CD163+, CD206+). Responders showed increased M1-like macrophages, whereas non-responders displayed reduced M1-features. An increase in DC3-like cells was observed in non-responders following treatment. Conclusions: This single-cell spatial atlas reveals shared and subtype-specific immune features in MF\/SS. Th2-skewed malignant T-cell status and myeloid polarization correlate with clinical response, supporting their potential as spatial biomarkers for patient stratification in mogamulizumab therapy.<\/jats:p>","DOI":"10.3390\/cancers18142348","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:14:27Z","timestamp":1784621667000},"page":"2348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dissecting Immune Determinants in Lesional Skin of Cutaneous T-Cell Lymphoma During Mogamulizumab Therapy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-446X","authenticated-orcid":false,"given":"Xiao","family":"Ni","sequence":"first","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niharika","family":"Kunta","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghali","family":"Goswami","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-9074","authenticated-orcid":false,"given":"Jared K.","family":"Burks","sequence":"additional","affiliation":[{"name":"Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Duvic","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2200039","DOI":"10.1002\/prca.202200039","article-title":"Tape stripped stratum corneum samples are suitable for diagnosis and comprehensive proteomic investigation in mycosis fungoides","volume":"17","author":"Qureshi","year":"2023","journal-title":"Proteom. Clin. Appl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9237381","DOI":"10.1155\/2020\/9237381","article-title":"Proteomic Profiling Change and Its Implies in the Early Mycosis Fungoides (MF) Using Isobaric Tags for Relative and Absolute Quantification (iTRAQ)","volume":"2020","author":"Zhu","year":"2020","journal-title":"BioMed Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1158\/1078-0432.CCR-14-0830","article-title":"Reduction of regulatory T cells by Mogamulizumab, a defucosylated anti-CC chemokine receptor 4 antibody, in patients with aggressive\/refractory mycosis fungoides and Sezary syndrome","volume":"21","author":"Ni","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1182\/blood-2014-09-600924","article-title":"Phase 1\/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma","volume":"125","author":"Duvic","year":"2015","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ijsselsteijn, M.E., van der Breggen, R., Farina Sarasqueta, A., Koning, F., and de Miranda, N. (2019). A 40-Marker Panel for High Dimensional Characterization of Cancer Immune Microenvironments by Imaging Mass Cytometry. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02534"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Le Rochais, M., Hemon, P., Pers, J.O., and Uguen, A. (2022). Application of High-Throughput Imaging Mass Cytometry Hyperion in Cancer Research. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.859414"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103079","DOI":"10.1016\/j.xpro.2024.103079","article-title":"Protocol to quantify immune cell distribution from the vasculature to the glioma microenvironment on sequential immunofluorescence multiplex images","volume":"5","author":"Najem","year":"2024","journal-title":"STAR Protoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9033","DOI":"10.1038\/s41467-024-53262-w","article-title":"Spatial dynamics of CD39(+)CD8(+) exhausted T cell reveal tertiary lymphoid structures-mediated response to PD-1 blockade in esophageal cancer","volume":"15","author":"Tanoue","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1016\/j.csbj.2024.10.048","article-title":"PENGUIN: A rapid and efficient image preprocessing tool for multiplexed spatial proteomics","volume":"23","author":"Sequeira","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1038\/s41588-024-01961-x","article-title":"Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer\u2019s disease","volume":"56","author":"Miyoshi","year":"2024","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1038\/s41467-025-61023-6","article-title":"ADTnorm: Robust integration of single-cell protein measurement across CITE-seq datasets","volume":"16","author":"Zheng","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/0190-9622(92)70297-S","article-title":"Mycosis fungoides\u2013type cutaneous T-cell lymphoma arising before 30 years of age. Immunophenotypic, immunogenotypic and clinicopathologic analysis of nine cases","volume":"27","author":"Burns","year":"1992","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nakamizo, S., Dutertre, C.A., Khalilnezhad, A., Zhang, X.M., Lim, S., Lum, J., Koh, G., Foong, C., Yong, P.J.A., and Tan, K.J. (2021). Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis. J. Exp. Med., 218.","DOI":"10.1084\/jem.20202345"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/imm.12888","article-title":"Human dendritic cell subsets: An update","volume":"154","author":"Collin","year":"2018","journal-title":"Immunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/jid.2013.481","article-title":"A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels","volume":"134","author":"Wang","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3732","DOI":"10.1182\/blood.2021014468","article-title":"Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma","volume":"139","author":"Beygi","year":"2022","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1038\/s41590-024-02018-1","article-title":"Cutaneous T cell lymphoma atlas reveals malignant T(H)2 cells supported by a B cell-rich tumor microenvironment","volume":"25","author":"Li","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1172\/JCI32282","article-title":"Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages","volume":"117","author":"Zaba","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nri3683","article-title":"The origins and functions of dendritic cells and macrophages in the skin","volume":"14","author":"Malissen","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.immuni.2016.02.024","article-title":"Tissue-Resident Macrophage Ontogeny and Homeostasis","volume":"44","author":"Ginhoux","year":"2016","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1038\/jid.2014.206","article-title":"Depletion of M2-like tumor-associated macrophages delays cutaneous T-cell lymphoma development in vivo","volume":"134","author":"Wu","year":"2014","journal-title":"J. Investig. Dermatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.jid.2019.11.018","article-title":"A Small Molecule CCR2 Antagonist Depletes Tumor Macrophages and Synergizes with Anti-PD-1 in a Murine Model of Cutaneous T-Cell Lymphoma (CTCL)","volume":"140","author":"Wu","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1182\/blood.2021013341","article-title":"Macrophage-derived CXCL9 and CXCL11, T-cell skin homing, and disease control in mogamulizumab-treated CTCL patients","volume":"139","author":"Darbord","year":"2022","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cytogfr.2007.10.008","article-title":"Tumor-induced modulation of dendritic cell function","volume":"19","author":"Gottfried","year":"2008","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2350891","DOI":"10.1002\/eji.202350891","article-title":"cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model","volume":"54","author":"Subtil","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/intimm\/11.1.81","article-title":"Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine","volume":"11","author":"Imai","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13045-024-01559-0","article-title":"Deciphering the performance of macrophages in tumour microenvironment: A call for precision immunotherapy","volume":"17","author":"Toledo","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Guo, N., Jia, L., Out-Luiting, C., Miranda, N., Willemze, R., Koning, F., Vermeer, M., and Quint, K. (2022). Mass Cytometric Analysis of Early-Stage Mycosis Fungoides. Cells, 11.","DOI":"10.3390\/cells11071062"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1080\/1744666X.2025.2507332","article-title":"Mycosis fungoides and IL-4\/13 inhibitors: What is known and unmet needs","volume":"21","author":"Guglielmo","year":"2025","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1158\/1078-0432.CCR-24-1660","article-title":"Facts and Hopes of CD40 Agonists in Cancer Immunotherapy","volume":"31","author":"McVey","year":"2025","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41551-018-0236-8","article-title":"TLR7\/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy","volume":"2","author":"Rodell","year":"2018","journal-title":"Nat. Biomed. Eng."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/14\/2348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:28:39Z","timestamp":1784622519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/14\/2348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":32,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cancers18142348"],"URL":"https:\/\/doi.org\/10.3390\/cancers18142348","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}