CCR4 + T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16

Tuzova, Marina; Richmond, Julius B.; Wolpowitz, Deon; Curiel‐Lewandrowski, Clara; Chaney, Keri; Kupper, Thomas S.; Cruikshank, William W.

doi:10.3109/10428194.2014.919634

Cited by 26 publications

(26 citation statements)

References 43 publications

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“…However, similar to CXCL9 and CXCL10, the expression of CXCR3 also decreases during disease progression, which is accompanied by a gradual loss of epidermotropism [12, 13, 45]. In contrast, CCR4, the receptor for CCL17 and CCL22, is continuously expressed by the malignant T cells and, in line with the upregulation of CCL17 and CCL22, the number of CCR4-positive T cells increases in later disease stages [10, 47, 49]. A recent phase I/II clinical study of the humanized anti-CCR4 antibody, mogamulizumab, showed promising results in heavily pretreated patients, supporting an important role of the CCR4-CCL17/CCL22 axis in the pathogenesis of CTCL [54].…”

Section: Changes In the Chemokine Profile Facilitate The Development mentioning

confidence: 99%

“…IL-16 is a growth factor and a chemo-attractant for CD4 + T cells. Accordingly, evidence supports that elevated levels of IL-16 contribute to the cutaneous accumulation of the malignant T cells by augmenting their intradermal proliferation and potentiating their recruitment into the skin [49, 69]. The expression of IL-17A and IL-17F is heterogeneous and confined to a subset of patients which is likely the cause of discrepant reports regarding their expression in CTCL [55, 62, 70–73].…”

Section: The Expression Of Pro-tumorigenic Cytokines Increases Duringmentioning

confidence: 99%

“…These findings imply that IL-4 and IL-13 produced by malignant T cells and benign Th2 cells stimulate the proliferation of the malignant T cells via activation of Stat6. Other cytokines that are upregulated in advanced disease, including IL-15, IL-16, and IL-32, can also augment the growth of the malignant T cells in an autocrine manner [49, 59, 61, 64, 65, 114]. Of particular interest, IL-15 activates Stat5 and Stat3 in malignant CTCL cells and has been proposed to contribute to the aberrant activation of these transcription factors [43, 108, 115].…”

Section: The Malignant T Cells Produce Autocrine Growth Factors That mentioning

confidence: 99%

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Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

et al. 2016

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Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term “malignant inflammation” as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL.

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Section: Changes In the Chemokine Profile Facilitate The Development mentioning

confidence: 99%

Section: The Expression Of Pro-tumorigenic Cytokines Increases Duringmentioning

confidence: 99%

Section: The Malignant T Cells Produce Autocrine Growth Factors That mentioning

confidence: 99%

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Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

et al. 2016

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“…The three Hodgkin lymphoma patients and the mycosis fungoides patient developed progressive neurological deterioration and died soon after the development of the PML [53 & ]. Chemokine receptor 4 (CCR4) is expressed by T cells and is important for their recruitment to the skin [54]. Mogamulizumab is a monoclonal antibody against CCR4 that has been developed for the treatment of diverse hematological malignancies and asthma [55].…”

Section: The European Organization For Research and Treatment Of Cancermentioning

confidence: 99%

Recent advances in primary cutaneous T-cell lymphoma

DeSimone

Sodha

Ignatova

et al. 2015

Current Opinion in Oncology

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PURPOSE OF REVIEW Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. RECENT FINDINGS In the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SUMMARY This is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year. Purpose of review Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. Recent findingsIn the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SummaryThis is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year.

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“…5 Recently, the association of thymic stromal lymphopoietin (TSLP) with tumor survival and progression of several kinds of tumors, such as breast, lung, gastric, pancreatic, and cervical cancers, and mycosis fungoides have been reported. [10][11][12] The TSLP receptor (TSLPR) complex has also been found in pediatric B-cell acute lymphocytic leukemia. 10 Although TSLPR expression is observed in multiple myeloma cell lines, TSLP does not affect the proliferation or drug resistance of multiple myeloma cells.…”

Section: Detection Of Minimal Bone Marrow Involvement Of Blastic Plasmentioning

confidence: 99%

Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool-

Ohe

Aung

Shiono

et al. 2018

J Clin Exp Hematopathol

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JC EH lin xp ematopathol Original article INTRODUCTIONBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a relatively rare hematological malignancy, 1 accounting for 0.44% of all hematological malignancies and 0.7% of all cutaneous lymphomas.2 BPDCN is a clinically aggressive tumor derived from the precursors of plasmacytoid dendritic cells (pDC).1 It usually occurs at the age of 50-70 and is rare in pediatric patients; the ratio of male to female patients is 2.5-2.7:1, and the median survival is 12-14 months. 1-4The clinical features and evolution of BPDCN are rather homogenous and categorized into dermatopathic (>90% of cases) and leukemic patterns. 5 The dermatopathic pattern is characterized by a deceptive indolent onset dominated by skin lesions, which is the prominent and only detectable clinical feature in nearly 50% of patients, followed by tumor dissemination. Conversely, the leukemic variant is characterized by an elevated white blood cell count, circulating neoplastic cells, and massive bone marrow (BM) infiltration. Pure leukemic presentation is very rare (7% of 756 cases) and is mostly associated with multiple skin lesions. Other manifestations are related with tumor infiltration into the lymph nodes (localized and generalized lymphadenopathy), spleen, and liver. Notably, BPDCN can be precisely diagnosed by the immunohistochemical scoring system using CD4, CD56, and Blastic plasmacytoid dendritic cell (pDC) neoplasm (BPDCN) is a relatively rare hematological malignancy with significantly complex clinicopathological features that are still unclear. This study aimed to analyze the clinicopathological data of BPDCN and evaluate immunohistochemical detection of minimal bone marrow (BM) involvement. In this study, we examined skin and BM lesions from 6 patients with BPDCN. Neoplastic cells tested positive for CD303 (polyclonal, 100%; monoclonal, 40%) in the skin lesions and for CD303 (polyclonal, 100%; monoclonal, 67%) in the BM clots. Although immunostaining of CD4, CD56, CD123, CD303, and TCLl detected minimal BM involvement in 3 patients, morphological identification was challenging in the BM clots stained with hematoxylin-eosin. In conclusion, our results demonstrate the significance of observing BM smears to detect neoplastic cells and that immunohistochemical examination, including CD303 antibodies, is useful to detect minimal BM involvement. This study is the first to report the expression of thymic stromal lymphopoietin (TSLP) and its receptor in BPDCN cells. Therefore, the TSLP/TSLP receptor axis may be associated with the proliferation of BPDCN, and consequently, the survival of patients.

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CCR4 + T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16

Cited by 26 publications

References 43 publications

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

Malignant inflammation in cutaneous T‐cell lymphoma—a hostile takeover

Recent advances in primary cutaneous T-cell lymphoma

Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool-

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