Cancers, Vol. 12, Pages 377: Selective Killing of Activated T Cells by 5-Aminolevulinic Acid Mediated Photodynamic Effect: Potential Improvement of Extracorporeal Photopheresis

In this study, we used the concept of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor of an endogenously synthesized photosensitizer protoporphyrin IX (PpIX) in combination with blue light to explore the possibility of targeting activated human blood T cells ex vivo. With various T-cell activation protocols, a high ALA-induced PpIX production took place in activated CD3+, CD4+CD25+, and CD8+ T cell populations with their subsequent killing after blue light exposure. By contrast, resting T cells were much less damaged by the treatment. The selective and effective killing effect on the activated cells was also seen after co-cultivating activated and resting T cells. Under our clinically relevant experimental conditions, ALA-PDT killed activated T cells more selectively and efficiently than 8-MOP/UV-A. Monocyte-derived dendritic cells (DCs) were not affected by the treatment. Incubation of ALA-PDT damaged T cells with autologous DCs induced a downregulation of the co-stimulatory molecules CD80/CD86 and also upregulation of interleukin 10 (IL-10) and indoleamine 2,3-dioxygenase expression, two immunosuppressive factors that may account for the generation of tolerogenic DCs. Overall, the data support the potential use of ALA-PDT strategy for improving ECP by selective and effective killing of activated T cells and induction of immune tolerance.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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de Masson Cutaneous T-cell lymphomas (CTCLs) are non-Hodgkin lymphomas that develop primarily in the skin. They account for almost 80% of primary cutaneous lymphomas. Epidermotropic CTCLs (mycosis fungoides (MF) and Sézary syndrome (SS)) are the most common form of CTCL. The course of the disease ranges from an indolent clinical behavior in early-stage disease to an aggressive evolution in the advanced stages. Advanced-stage disease is defined by the presence of tumors, erythroderma, or significant blood, nodal or visceral involvement. Advanced-stage disease is characterized by frequent disease relapses, re...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Patients with cutaneous T-cell lymphoma (CTCL) are at increased risk of developing Hodgkin lymphoma, non-Hodgkin lymphoma, lung and bladder cancer, and melanoma Annual total body skin exams are needed in CTCL patients to screen for melanoma. New malignancy screening protocols for CTCL patients are needed
Source: Journal of the American Academy of Dermatology - Category: Dermatology Authors: Source Type: research
iles Prince Time to next treatment (TTNT) is an emerging endpoint in clinical studies of primary cutaneous T-cell lymphomas (CTCL), with utility as a surrogate marker for the “duration of clinical benefit”. TTNT provides a highly clinically meaningful endpoint that uniquely reflects not only the duration of treatment efficacy on disease and symptom control, but also incorporates the patient experience by accounting for patient compliance and tolerance to the studied therapy(s). Given the distinct challenges of pin-pointing the exact date of progression in patients with multi-compartmental CTCL, TTNT...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Perspective Source Type: research
Cancers, Vol. 12, Pages 2293: Phase I/Ib Study of Tenalisib (RP6530), a Dual PI3K δ/γ Inhibitor in Patients with Relapsed/Refractory T-Cell Lymphoma Cancers doi: 10.3390/cancers12082293 Authors: Auris Huen Bradley M. Haverkos Jasmine Zain Ramchandren Radhakrishnan Mary Jo Lechowicz Sumana Devata Neil J. Korman Lauren Pinter-Brown Yasuhiro Oki Prajak J. Barde Ajit Nair Kasi Viswanath Routhu Srikant Viswanadha Swaroop Vakkalanka Swaminathan P. Iyer Tenalisib (RP6530), a dual phosphoinositide 3-kinase δ/γ inhibitor was evaluated in a phase I/Ib study for maxi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions: Epigenetic silencing and other as yet unknown mechanisms repress TXNIP expression in malignant T cells. As forced expression of TXNIP inhibits malignant proliferation, we propose that TXNIP is a putative tumour suppressor in CTCL.Dermatology
Source: Dermatology - Category: Dermatology Source Type: research
This study sought to characterize CAFs in MF and their cross talk with the lymphoma cells using primary fibroblast cultures from punch biopsies of patients with early-stage MF and healthy subjects. MF cultures yielded significantly increased levels of FAP α, a CAF marker, and CAF-associated genes and proteins: CXCL12 (ligand of CXCR4 expressed on MF cells), collagen XI, and MMP2.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
ka Cutaneous T-cell lymphomas (CTCLs) represent a large, heterogeneous group of non-Hodgkin lymphomas that primarily affect the skin. Among multiple CTCL variants, the most prevalent types are mycosis fungoides (MF) and Sézary syndrome (SS). In the past decade, the molecular genetics of CTCL have been the target of intense study, increasing the knowledge of CTCL genomic alterations, discovering novel biomarkers, and potential targets for patient-specific therapy. However, the detailed pathogenesis of CTCL development still needs to be discovered. This review aims to summarize the novel insights into molecula...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Hernández Salazar Litvinov Hypopigmented mycosis fungoides (HMF) is a form of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin’s lymphomas. HMF has a unique set of defining features that include light colored to achromic lesions, a predilection for darker skin phototypes, an early onset of disease, and predominance of CD8+ T-cells, among others. In the current review, we detail the known pathways of molecular pathogenesis for this lymphoma and posit that an active Th1/cytotoxic antitumor immune response in part explains why this variant is primarily seen in child...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
We present here a unique pediatric case of transformed mycosis fungoides in a patient with BRCA2 mutation.
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
Mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma (CTCL), may undergo large cell transformation (LCT), which is related to aggressive clinical courses and resistance to conventional treatments. However, the mechanisms of LCT remain largely unknown. To explore the molecular pathogenesis underlying the transformation of MF, we performed whole-transcriptome sequencing (RNA-seq) followed by integrated deep analyses on lesional biopsies from 49 tumor-stage MF patients, including 26 patients with LCT and 23 patients without LCT (NLCT).
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
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