Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042

Urosevic-Maiwald, Mirjana; Dummer, Reinhard; Bataille, Vincent; Kehrer, Nadine; Niculescu, Cristina; Limacher, Jean‐Marc; Chenard, Marie–Pierre; Bonnefoy, Jean‐Yves; Rooke, Ronald

doi:10.1186/1479-5876-11-226

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…Promising results were obtained in a study where prophylactic treatment with IFN-γ prevented recurrence of bladder tumor after transurethral tumor resection [ 39 ]. Equally promising results IFN-γ1b used for treatment of patients with adult T cell leukemia have been reported capable of inducing lasting remissions [ 40 ], while administration of adenovirus vectors that express IFN-γ cDNA showed a clinical benefit for patients with cutaneous T and B cell lymphomas [ 41 , 42 ]. IFN-γ treatments led to upregulated human leukocyte antigen-D related (HLA-DR) expression, a human MHC class II molecule, and improved prognosis of colorectal patients [ 43 ].…”

Section: Ifn-γ In Clinical Settingsmentioning

confidence: 99%

The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion

Mojić

Takeda

Hayakawa

2017

IJMS

269

189

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Interferon-γ (IFN-γ) is a pleiotropic cytokine that has long been praised as an important effector molecule of anti-tumor immunity, capable of suppressing tumor growth through various mechanisms. On the contrary to such a bright side of IFN-γ, it has also been involved in promoting an outgrowth of tumor cells with immunoevasive phenotype suggesting an existence of a dark “tumor-promoting” side effect of IFN-γ. In this review, we will summarize this multi-functional role of IFN-γ in tumor context, how it promotes changes in tumor phenotype towards increased fitness for growth in immunocompetent host. Furthermore, we summarize how IFN-γ is involved in homeostatic or cancer-triggered mechanisms to establish an immunosuppressive tumor microenvironment.

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Section: Ifn-γ In Clinical Settingsmentioning

confidence: 99%

The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion

Mojić

Takeda

Hayakawa

2017

IJMS

269

189

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“…The shift from a Th1- to a Th2-biased tumor microenvironment ( Figure 1 ) is thought to play a critical role in the transition from indolent to progressive disease by impairing cellular anti-tumor responses whilst fostering the proliferation of malignant T cells. Indeed, administration of Toll-like receptor (TLR) agonists boosting cellular immunity has shown clinical efficacy, and treatment with IL-12 and IFNγ can induce regression of CTCL lesions which is associated with increased numbers of CD8 T cells in the resolving skin ( Rook et al, 1999 , 2001 , 2015 ; Suchin et al, 2002 ; Dummer et al, 2004 ; Duvic et al, 2006 ; Wysocka et al, 2007 ; Kim et al, 2010 ; Accart et al, 2013 ). Of notice, recent case reports have surprisingly described that long-term treatment with dupilumab, a neutralizing antibody targeting IL-4 receptor alpha, may exacerbate CTCL and possibly even trigger the disease in certain patients with severe atopic dermatitis (AD) ( Chiba et al, 2019 ; Espinosa et al, 2020 ; Miyashiro et al, 2020 ; Tran et al, 2020 ; Umemoto et al, 2020 ).…”

Section: Th2-bias During Disease Progressionmentioning

confidence: 99%

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

Stolearenco

Namini

Hasselager

et al. 2020

Front. Cell Dev. Biol.

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Cutaneous T-cell lymphoma (CTCL) comprises a group of lymphoproliferative diseases characterized by the accumulation of malignant T cells in chronically inflamed skin lesions. In early stages, the disease presents as skin patches or plaques covering a limited area of the skin and normally follows an indolent course. However, in a subset of patients the cutaneous lesions develop into tumors and the malignant T cells may spread to the lymphatic system, blood and internal organs with fatal consequences. Despite intensive research, the mechanisms driving disease progression remain incompletely understood. While most studies have focused on cancer cell-intrinsic oncogenesis, such as genetic and epigenetic events driving malignant transformation and disease progression, an increasing body of evidence shows that the interplay between malignant T cells and non-malignant cells plays a crucial role. Here, we outline some of the emerging mechanisms by which tumor, stromal and epidermal interactions may contribute to the progression of CTCL with particular emphasis on the crosstalk between fibroblasts, keratinocytes and malignant T cells.

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“…Although higher doses of IFN-α demonstrate greater anti-tumor activity, its significant systemic toxicities result in a very narrow therapeutic index (low maximum tolerated dose vs high optimal therapeutic dose). To address this limitation, several strategies have been explored to selectively deliver IFN-α to the tumor itself, including: (1) immunocytokines; (2) genetically modified DCs expressing IFN-α; (3) viral and other tumor-targeting vectors encoding IFN-α [ 40 – 43 ]; and (4) vectors encoding pattern recognition receptor agonists delivered directly into tumor microenvironment. One major strategy currently under pre-clinical development aims to target IFN-α to specific cell populations (such as malignant cells or specific types of leukocytes) by conjugating IFN-α to mAbs to generate antibody-based IFN-α fusion proteins, also called immunocytokines or immunoconjugates.…”

Section: Ifn-α-targeted Immunocytokines In B Cell Lymphoma and Myelommentioning

confidence: 99%

Interferon-alpha-based immunotherapies in the treatment of B cell-derived hematologic neoplasms in today’s treat-to-target era

Zhang

Tai

et al. 2017

Exp Hematol Oncol

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B cell lymphoma and multiple myeloma (MM) are the most common hematological malignancies which benefit from therapeutic monoclonal antibodies (mAbs)-based immunotherapies. Despite significant improvement on patient outcome following the use of novel therapies for the past decades, curative treatment is unavailable for the majority of patients. For example, the 5-year survival of MM is currently less than 50%. In the 1980s, interferon-α was used as monotherapy in newly diagnosed or previously treated MM with an overall response rate of 15–20%. Noticeably, a small subset of patients who responded to long-term interferon-α further achieved sustained complete remission. Since 1990, interferon-α-containing regimens have been used as a central maintenance strategy for patients with MM. However, the systemic administration of interferon-α was ultimately limited by its pronounced toxicity. To address this, the selective mAb-mediated delivery of interferon-α has been developed to enhance specific killing of MM and B-cell malignant cells. As such, targeted interferon-α therapy may improve therapeutic window and sustain responses, while further overcoming suppressive microenvironment. This review aims to reinforce the role of interferon-α by consolidating our current understanding of targeting interferon-α with tumor-specific mAbs for B cell lymphoma and myeloma.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-017-0081-6) contains supplementary material, which is available to authorized users.

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Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042

Cited by 10 publications

References 23 publications

The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion

The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion

Cellular Interactions and Inflammation in the Pathogenesis of Cutaneous T-Cell Lymphoma

Interferon-alpha-based immunotherapies in the treatment of B cell-derived hematologic neoplasms in today’s treat-to-target era

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