Immunobiology and treatment of cutaneous T-cell lymphoma.

Introduction: Primary cutaneous T cell lymphomas (CTCL) are a heterogenous group of non-Hodgkin lymphomas derived from skin-homing T cells. These include mycosis fungoides and its leukemic variant Sezary syndrome, as well as the CD30+ lymphoproliferative disorders.

Areas Covered: In this review, we provide a summary of the current literature on CTCL, with a focus on the immunopathogenesis and treatment of mycosis fungoides and Sezary syndrome.

Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma.

A challenge when targeting T-cell lymphoma with chimeric antigen receptor (CAR) T-cell therapy is that target antigens are often shared between T cells and tumor cells, resulting in fratricide between CAR T cells and on-target cytotoxicity on normal T cells. CC chemokine receptor 4 (CCR4) is highly expressed in many mature T-cell malignancies, such as adult T-cell leukemia/lymphoma (ATLL) and cutaneous T-cell lymphoma (CTCL), and has a unique expression profile in normal T cells. CCR4 is predominantly expressed by type-2 and type-17 helper T cells (Th2 and Th17) and regulatory T cells (Treg), but it is rarely expressed by other T helper (Th) subsets and CD8+ cells.

TCRvβ-CART therapy mediates high-precision targeting of malignant T-cell clones.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoid malignancies associated with poor prognosis due to ineffective treatment options and high rates of relapse. The success of chimeric antigen receptor T-cell (CART) therapy for certain hematologic malignancies makes it an attractive treatment option for PTCLs. However, shared expression of potential target antigens by both malignant and healthy T cells poses a challenge.

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial.

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).

The Robust Tumoricidal Effects of Combined BET/HDAC Inhibition in Cutaneous T-Cell Lymphoma Can Be Reproduced by ΔNp73 Depletion.

Combined BET inhibitor/histone deacetylase inhibitor treatment induces marked apoptosis of cutaneous T-cell lymphoma (CTCL) with minimal normal T-cell toxicity. At 96 hours when apoptosis was extensive, a majority of CTCL lines showed ≥2-fold suppression of T-cell survival factors (e.g.

Management of relapsed cutaneous T-Cell lymphoma following allogeneic hematopoietic stem cell transplantation: Review with representative patient case.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option for patients with refractory cutaneous T-cell lymphoma (CTCL) through replacement of the bone marrow responsible for lymphoma cells and possibly induction of a graft-versus-lymphoma effect. However, allo-HSCT is not always curative; relapse of CTCL occurs in about half of patients post-transplant. Treatment of relapsed CTCL after allo-HSCT is challenging because post-transplant patients are at high risk of graft-versus-host disease, and this condition may be precipitated or exacerbated by standard CTCL therapies.

Resistance to mogamulizumab is associated with loss of CCR4 in cutaneous T-cell lymphoma.

Mogamulizumab is a humanized anti-CC chemokine receptor 4 (CCR4) antibody approved for the treatment of mycosis fungoides and Sézary syndrome. Despite almost universal expression of CCR4 in these diseases, most patients eventually develop resistance to mogamulizumab. We tested whether resistance to mogamulizumab is associated with loss of CCR4 expression.

Dermatologic Events Associated with the Anti-CCR4 Antibody Mogamulizumab: Characterization and Management.

The CCR4-directed monoclonal antibody mogamulizumab has been shown to significantly improve progression-free survival and overall response rate compared with vorinostat in adults with relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS). One of the most common adverse events seen with mogamulizumab in MF/SS patients is rash. Because of the protean nature of MF/SS and the variable clinical and histopathological features of mogamulizumab-associated rash, healthcare providers may have difficulty distinguishing rash from disease, and may not be aware of appropriate treatment strategies for this generally manageable adverse event.

Canine thyroid carcinoma prognosis following the utilisation of computed tomography assisted staging.

Background: Metastatic disease is frequently present at the time of diagnosis of canine thyroid carcinoma; however, utilisation of computed tomography (CT) alone for staging pre-treatment has been rarely reported in the veterinary literature.

Methods: The aims of this retrospective study were to stage affected dogs using CT findings of the cervical and thoracic regions, combined with histopathology/cytology results, in order to assess whether metastatic disease/WHO staging was of prognostic significance.

Results: Fifty-eight dogs were included in the study.

Bipolar ablation's unique paradigm: Duration and power as respectively distinct primary determinants of transmurality and steam pop formation.

Background: Bipolar radiofrequency (RF) ablation strategies are increasingly used, mainly to target deep myocardial reentrant circuits responsible for ventricular tachycardia that cannot be extinguished with traditional unipolar RF ablation. Because this strategy is novel, factors that affect lesion geometry and steam pop formation require further investigation.

Objective: To assess the effect of contact force, power, and time on the resulting lesion geometry and the risk of steam pop formation during bipolar RF ablation of thick myocardial tissue.

An initial ex vivo evaluation of temperature profile and thermal injury formation on the epiesophageal surface during radiofrequency ablation.

Introduction: Few studies have examined heat transfer and thermal injury on the epiesophageal surface during radiofrequency application, or compared the risk of esophageal thermal injury between standard and high-power, short-duration (HPSD) ablation. We studied the thermodynamics of HPSD and standard ablation at different tissue interfaces between the left atrium and esophagus, focusing on epiesophageal temperature changes and thermal injury.

Methods And Results: Fresh porcine heart and esophageal sections were secured to a custom holder and submerged in a temperature-controlled, circulating water bath.

Alcohol Ablation of Cardiac Tissues Quantified and Evaluated Using CIELAB Euclidean Distances.

Ethanol solubilizes cell membranes, making it useful for various ablation applications. We examined the effect of time and alcohol type on the extent of ablation, quantified as Euclidean distances between color coordinates. We obtained biopsy punch samples (diameter, 6 mm) of left atrial appendage, atrial, ventricular, and septal tissue from porcine hearts and placed them in transwell plates filled with ethanol or methanol for 10, 20, 30, 40, 50, or 60 min.

Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome.

Importance: Treatment options for Sézary syndrome (SS) are limited and associated with low response rates. Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for refractory CD30-positive cutaneous T-cell lymphoma. However, limited data exist on its efficacy in SS, including in the pivotal phase 3 ALCANZA (A Phase 3 Trial of Brentuximab Vedotin (SGN-35) Versus Physician's Choice [Methotrexate or Bexarotene] in Participants With CD30-Positive Cutaneous T-Cell Lymphoma) trial.

The immunopathogenesis and immunotherapy of cutaneous T cell lymphoma: Current and future approaches.

In the past few decades, immunotherapy has emerged as an effective therapeutic option for patients with cutaneous T cell lymphoma (CTCL). CTCL is characterized by progressive impairment of multiple arms of the immune system. Immunotherapy targets these deficits to stimulate a more robust antitumor response, thereby both clearing the malignant T cells and repairing the immune dysfunction.