-
Nature Communications Nov 2021Cutaneous 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...
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.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; CD4-Positive T-Lymphocytes; Female; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphocyte Activation; Lymphoma, T-Cell, Cutaneous; Male; Middle Aged; Mycosis Fungoides; Programmed Cell Death 1 Receptor; Sezary Syndrome; Skin Neoplasms; Treatment Outcome
PubMed: 34795254
DOI: 10.1038/s41467-021-26974-6 -
Blood Jan 2023
Topics: Humans; Adenosine; T-Lymphocytes; Sezary Syndrome; Adenosine Triphosphate; Skin Neoplasms; Immunosuppression Therapy
PubMed: 36602823
DOI: 10.1182/blood.2022018185 -
Blood Oct 2021
Topics: Flow Cytometry; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34673947
DOI: 10.1182/blood.2021012016 -
Indian Journal of Dermatology 2023Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic...
Dupilumab is a monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13), approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). While recent reports have described cases of new-onset mycosis fungoides (MF) following treatment with dupilumab for AD, to our knowledge only one patient has been delineated with the progression to SS. We present an additional case of a patient who was diagnosed with SS following treatment with dupilumab for adult-onset AD and asthma. We examine SS as a possible side effect of dupilumab while also discussing management and theories to explain this phenomenon.
PubMed: 37822402
DOI: 10.4103/ijd.ijd_580_22 -
Journal Der Deutschen Dermatologischen... Sep 2021Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL) with not yet fully understood etiology and pathogenesis. Conceptually, MF...
Mycosis fungoides (MF) and Sézary syndrome (SS) are primary cutaneous T-cell lymphomas (CTCL) with not yet fully understood etiology and pathogenesis. Conceptually, MF and SS are classified as distinct entities arising from different T helper cell subsets. MF is the most common CTCL entity, while SS is very rare. MF presents clinically with patch, plaque and/or tumor stages, but can also evolve as erythroderma, which in turn is pathognomonic for SS. SS is characterized by a detectable tumor-cell burden (Sézary cells) in the peripheral blood consistent with advanced-stage disease and a poor prognosis. In early-stage disease of MF, which is the predominant form, the prognosis is generally favorable. However, in up to 30 % of patients, there is progression of skin lesions, which can ultimately lead to visceral involvement. The histological manifestation of MF can be subtle in early-stage disease and therefore a careful clinicopathological correlation is paramount. The treatment of MF/SS is dependent on the disease stage. Therapeutic options include both skin-directed and systemic regimens. Apart from allogeneic stem cell transplantation (alloSCT), there is as yet no curative therapy for MF/SS. Accordingly, the treatment approach is symptom oriented and aims to reduce the tumor burden and improve health-related quality of life. However, the therapeutic landscape for CTCL is constantly being expanded by the discovery of novel therapeutic targets.
Topics: Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Quality of Life; Sezary Syndrome; Skin Neoplasms
PubMed: 34541796
DOI: 10.1111/ddg.14610 -
Blood Dec 2021
Topics: Gene Expression Profiling; Humans; Sezary Syndrome; Skin Neoplasms
PubMed: 34914833
DOI: 10.1182/blood.2021013433 -
International Journal of Molecular... Mar 2022Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic... (Review)
Review
Epigenetic modifications rarely occur in isolation (as single "epigenetic modifications"). They usually appear together and form a network to control the epigenetic system. Cutaneous malignancies are usually affected by epigenetic changes. However, there is limited knowledge regarding the epigenetic changes associated with cutaneous lymphomas. In this review, we focused on cutaneous T-cell lymphomas such as mycosis fungoides, Sézary syndrome, and anaplastic large cell lymphoma. With regard to epigenetic changes, we summarize the detailed chemical modifications categorized into DNA methylation and histone acetylation and methylation. We also summarize the epigenetic modifications and characteristics of the drug for cutaneous T-cell lymphoma (CTCL). Furthermore, we discuss current research on epigenetic-targeted therapy against cutaneous T-cell lymphomas. Although the current method of treatment with histone deacetylase inhibitors does not exhibit sufficient therapeutic benefits in all cases of CTCL, epigenetic-targeted combination therapy might overcome this limitation for patients with CTCL.
Topics: Epigenesis, Genetic; Humans; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Skin Neoplasms
PubMed: 35408897
DOI: 10.3390/ijms23073538