CD47-blocking checkpoint inhibitor TTI-621 shows promising results for cutaneous T-cell lymphomas

A novel CD47-blocking checkpoint inhibitor has shown promising interim results in a multicenter Phase I trail for relapsed/refractory mycosis fungoides and Szary syndrome, the most common types of cu... Author: VJHemOnc Added: 10/02/2018
Source: Oncology Tube - Category: Cancer & Oncology Source Type: podcasts

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Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) primarily arising in the skin. Early diagnosis is difficult as the histology overlaps with features of inflammatory skin diseases. Even when the diagnosis is established there are no prognostic markers that predict whether the disease will be aggressive or indolent. Lastly, there are no curative treatments and MF will invariably relapse even after aggressive chemotherapy. The main objective of this study is to address the presence of intratumor heterogeneity in MF.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
Mycosis fungoides (MF) and S ézary syndrome (SS) represent common and uncommon entities among primary cutaneous T cell lymphomas (CTCL). TOX is overexpressed in both of these CTCL entities and is correlated with disease severity and prognosis. TOX is a DNA-binding protein, which enables it to regulate the expression of multipl e downstream genes either directly or indirectly, thus supporting the malignant behavior of T cells in ways that are still unclear. Few validated markers exist which can be used to help discriminate early stage MF from benign inflammatory skin conditions.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Carcinogenesis and Cancer Genetics Source Type: research
Mycosis fungoides and Sezary Syndrome are the most common types of cutaneous T-cell Lymphomas (CTCL) and are often characterized by a Th2-dominant phenotype. This Th2 microenvironment is advantageous for tumor cells but may cause higher susceptibility to infections. Indeed, it has been shown that Staphylococcus aureus (S. aureus) frequently colonizes the skin and nares of CTCL patients which can result in chronic and recurrent skin and systemic infections. Furthermore, patients colonized by S. aureus who were treated with antibiotics frequently show clinical improvement of their skin lesion, suggesting a possible functional role of S.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Innate Immunity, Microbiology, and Microbiome Source Type: research
We report here that low-dose radiation therapy (LDRT, 8 Gy) induced durable remissions of treated lesions. We hypothesized that treatment with LDRT may era dicate the malignant T cell clone within the treated site. To address this, we examined pre- and post-treatment biopsies from 20 lesional skin samples of 18 MF patients who received either 8 Gy LDRT (n=16) or topical steroids (n=4) with high-throughput T-cell receptor sequencing (HTS) of the TCRB ge ne to identify, quantify, and follow the malignant T cell clone.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Translational Studies Source Type: research
Conclusions Epidemiological studies have repeatedly helped identify definitive triggers for several diseases. As highlighted in this perspective report, previous studies strongly argue for the interplay between intrinsic factors and putative preventable extrinsic triggers/promoters for CTCL. Given the evidence of geographical regional clustering of CTCL patients, CTCL occurrence in unrelated family members and recent evidence implicating S. aureus in the pathogenesis/progression of CTCL, more research is needed to decipher the precise mechanism by which specific environmental exposures may be driving the pathogenesis of t...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This article both highlights difficult clinical scenarios and reviews the recommended treatment as provided by the NCCN guidelines and provides alternative therapy for lesions that are either difficult to treat because of the location or are recalcitrant to the recommended therapy. With suggestions for the apparent gaps in guidelines, providers can better treat patients who present with more complicated conditions.
Source: American Journal of Clinical Dermatology - Category: Dermatology Source Type: research
Erica S. Tarabadkar† and Michi M. Shinohara*† Division of Dermatology, University of Washington, Seattle, WA, United States Skin directed therapies (SDTs) serve important roles in the treatment of early stage cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF), as well as managing symptoms and improving quality of life of all stages. There are now numerous options for topical therapies that demonstrate high response rates, particularly in early/limited MF. Phototherapy retains an important role in treating MF, with increasing data supporting efficacy and long-term safety of both UVB and PUVA as ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Cioplea M, Caruntu C, Zurac S, Bastian A, Sticlaru L, Cioroianu A, Boda D, Jugulete G, Nichita L, Popp C Abstract Dendritic cells (DCs) are antigen-presenting cells with an important role in the innate and adaptive immune system. In skin lesions, cutaneous DCs (Langerhans cells, dermal DCs and plasmacytoid DCs) are involved in immune activation in inflammatory benign lesions, as well as in malignant lymphoid proliferations. Density and distribution of DCs in the dermal infiltrate can be helpful to differentiate benign, reactive infiltrate from malignant nature of the lymphoid population. We performed a ret...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Source: Cancer Management and Research - Category: Cancer & Oncology Tags: Cancer Management and Research Source Type: research
More News: Cancer & Oncology | Cutaneous T cell lymphoma | Lymphoma | Mycosis Fungoides | T-cell Lymphoma