Spatially Guided and Single Cell Tools to Map the Microenvironment in Cutaneous T-Cell Lymphoma

Author:

Kalliara Eirini1ORCID,Belfrage Emma2ORCID,Gullberg Urban3,Drott Kristina3,Ek Sara1ORCID

Affiliation:

1. Department of Immunotechnology, Faculty of Engineering (LTH), University of Lund, 223 63 Lund, Sweden

2. Department of Dermatology and Venereology, Skane University Hospital (SUS), 205 02 Lund, Sweden

3. Department of Hematology and Transfusion Medicine, Skane University Hospital (SUS), 205 02 Lund, Sweden

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) are two closely related clinical variants of cutaneous T-cell lymphomas (CTCL). Previously demonstrated large patient-to-patient and intra-patient disease heterogeneity underpins the importance of personalized medicine in CTCL. Advanced stages of CTCL are characterized by dismal prognosis, and the early identification of patients who will progress remains a clinical unmet need. While the exact molecular events underlying disease progression are poorly resolved, the tumor microenvironment (TME) has emerged as an important driver. In particular, the Th1-to-Th2 shift in the immune response is now commonly identified across advanced-stage CTCL patients. Herein, we summarize the role of the TME in CTCL evolution and the latest studies in deciphering inter- and intra-patient heterogeneity. We introduce spatially resolved omics as a promising technology to advance immune-oncology efforts in CTCL. We propose the combined implementation of spatially guided and single-cell omics technologies in paired skin and blood samples. Such an approach will mediate in-depth profiling of phenotypic and molecular changes in reactive immune subpopulations and malignant T cells preceding the Th1-to-Th2 shift and reveal mechanisms underlying disease progression from skin-limited to systemic disease that collectively will lead to the discovery of novel biomarkers to improve patient prognostication and the design of personalized treatment strategies.

Funder

Swedish Cancer Foundation

Berta Kamprad Foundation

European Union’s Horizon 2020 Research and Innovation Program

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference90 articles.

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