Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia–lymphoma

Higuchi, Maho; Kuwatsuka, Yutaka; Murota, Hiroyuki; Iwanaga, Masako; Niino, Daisuke

doi:10.1016/j.prp.2018.10.001

Cited by 6 publications

(7 citation statements)

References 22 publications

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“…Few reports have been dedicated to studying the impact of cutaneous involvement in ATLL [2,8,9,[11][12][13]20]. Our results suggest that cutaneous involvement is associated with improved survival compared to non-cutaneous involvement, including aggressive ATLL forms.…”

Section: Discussionmentioning

confidence: 52%

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An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma

Malpica

Castro

Enríquez

et al. 2021

Leukemia & Lymphoma

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Adult T-cell leukemia/lymphoma (ATLL) is a largely incurable disease. Cutaneous involvement is common and could be first symptom of the disease. We analyzed 169 patients with ATLL of whom 63 had cutaneous involvement. Cutaneous involvement was found in 48, 27, 17, and 60% of acute, lymphomatous, chronic and smoldering ATLL cases, respectively. Eight cases had primary cutaneous tumoral variant. Erythroderma (24%) and plaques (22%) were the most frequent skin lesions. The presence of cutaneous involvement was associated with better overall survival compared to non-cutaneous involvement (aHR 0.55 [95% CI: 0.37-0.82], p < 0.01; 1-year OS 53 vs. 27%, respectively, p ¼ 0.012). Combination zidovudine and interferon-alpha (AZT-IFN) yielded high response rates (overall response, OR ¼ 100%, n ¼ 8; complete response 62.5%) compared to chemotherapy (OR ¼ 33.3%, n ¼ 12/36). In conclusion, cutaneous involvement was associated with better survival in Latin American patients with ATLL. AZT-IFN demonstrated encouraging responses in ATLL patients with cutaneous involvement.

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Section: Discussionmentioning

confidence: 52%

“…To date, data on the impact of cutaneous involvement on the clinical outcome of ATLL are limited [5,8,[11][12][13]. Aside from Brazil, no data from other Latin American countries where HTLV-1 infection is known to be endemic exist [3].…”

Section: Introductionmentioning

confidence: 99%

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma

Malpica

Castro

Enríquez

et al. 2021

Leukemia & Lymphoma

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“…Recently, Masaki et al 22 reported a significant correlation between higher HTLV-1 provirus load and higher percentage of PD-1 positive neoplastic T-cells in ATLL patients. Higuchi et al 23 evaluated 29 ATLL patients with skin lesions found that lesions with PD-1 expression over 50% have more advanced clinical type (nodulotumoral or erythrodermic) and histopathological pattern (nodular or diffuse) and possibly worse survival when compared to those with PD-1 expression under 50% cases, suggested PD-1 may serve as a biomarker to poor prognosis. Miyoshi et al 24 recently found that the expression of PD-L1 on neoplastic or stromal cells is a poor or good prognostic marker for ATLL, respectively.…”

Section: Prognostic Significance Of the Skin Lesions In Atllmentioning

confidence: 99%

Cutaneous Manifestations and Treatment Advances of Adult T-Cell Leukemia/Lymphoma

Zhang

Chen

Sun

2022

Int J Dermatol Venereol

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Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

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“…In the case of ATLL, it was reported that both neoplastic and normal CD4 + T cells in the peripheral blood of patients expressed PD-1 at increased levels compared with CD4 + T cells in the blood of normal healthy controls [ 214 ]. In 29 skin biopsy samples, PD-1 expression in neoplastic cells was found to be from 0% to 90% with the median values of 50% [ 215 ]. Furthermore, patients with a high PD-1 expression tended to have a shorter median survival time than those with a low PD-1 expression (18.2 months vs. 26.0 months) [ 215 ].…”

Section: Immune Checkpoint Inhibitors and Application Of Mogamulizumab In Solid Tumorsmentioning

confidence: 99%

“…In 29 skin biopsy samples, PD-1 expression in neoplastic cells was found to be from 0% to 90% with the median values of 50% [ 215 ]. Furthermore, patients with a high PD-1 expression tended to have a shorter median survival time than those with a low PD-1 expression (18.2 months vs. 26.0 months) [ 215 ]. Primary ATLL cells were also shown to express PD-L1 in a fraction of patients (21.7%).…”

Section: Immune Checkpoint Inhibitors and Application Of Mogamulizumab In Solid Tumorsmentioning

confidence: 99%

CCR4 as a Therapeutic Target for Cancer Immunotherapy

Yoshie

2021

Cancers

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CCR4 is a chemokine receptor mainly expressed by T cells. It is the receptor for two CC chemokine ligands, CCL17 and CCL22. Originally, the expression of CCR4 was described as highly selective for helper T type 2 (Th2) cells. Later, its expression was extended to other T cell subsets such as regulatory T (Treg) cells and Th17 cells. CCR4 has long been regarded as a potential therapeutic target for allergic diseases such as atopic dermatitis and bronchial asthma. Furthermore, the findings showing that CCR4 is strongly expressed by T cell malignancies such as adult T cell leukemia/lymphoma (ATLL) and cutaneous T cell lymphomas (CTCLs) have led to the development and clinical application of the fully humanized and glyco-engineered monoclonal anti-CCR4 Mogamulizumab in refractory/relapsed ATLL and CTCLs with remarkable successes. However, Mogamulizumab often induces severe adverse events in the skin possibly because of its efficient depletion of Treg cells. In particular, treatment with Mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo-HSCT), the only curative option of these T cell malignancies, often leads to severe glucocorticoid-refractory graft-versus-host diseases. The efficient depletion of Treg cells by Mogamulizumab has also led to its clinical trials in advanced solid tumors singly or in combination with immune checkpoint inhibitors. The main focus of this review is CCR4; its expression on normal and malignant T cells and its significance as a therapeutic target in cancer immunotherapy.

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Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia–lymphoma

Cited by 6 publications

References 22 publications

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma

An international, multicenter, retrospective study on the positive impact of cutaneous involvement on the clinical outcome of adult T-cell leukemia/lymphoma

Cutaneous Manifestations and Treatment Advances of Adult T-Cell Leukemia/Lymphoma

CCR4 as a Therapeutic Target for Cancer Immunotherapy

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