C‐C chemokine receptor 4 expression in CD8+ cutaneous T‐cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment

Abstract

Aims Patients with aggressive CD8+ cutaneous T‐cell lymphomas (CTCLs) progress rapidly and respond poorly to therapy. Confounding treatment planning, there is clinicopathological overlap between aggressive CD8+ CTCLs and other lymphoproliferative disorders (LPDs). Hence, improved diagnostic methods and therapeutic options are needed. The aim of this study was to examine C‐C chemokine receptor 4 (CCR4) expression as a diagnostic and therapeutic biomarker in CD8+ CTCLs/LPDs. Methods and results Forty‐nine cases (41 patients) with CD8+ CTCLs/LPDs were examined, including CD8+ mycosis fungoides (MF) (n = 14), aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma (AETCL) (n = 8), subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) (n = 7), CD30+ LPDs (n = 6), primary cutaneous γδ T‐cell lymphoma (GDTCL) (n = 6), and others (n = 8). Immunohistochemical tissue staining was performed with a CCR4 monoclonal antibody on formalin‐fixed paraffin‐embedded tissue sections. CCR4 immunostaining was graded as percentage infiltrate, i.e. high (>25%) and low (≤25%), and the results were correlated with clinicopathological diagnoses. CCR4 expression was seen in 69% of the studied cases. Any CCR4 positivity was seen in all CD8+ MF cases, in 83% of CD30+ LPD cases, in 75% of AETCL cases, in 33% of GDTCL cases, and in none of the SPTCL cases. High CCR4 expression was seen in 79% of CD8+ MF cases versus 33% of CD30+ LPD cases, in 17% of GDTCL cases, and in 12.5% of AETCL cases. Patients with more advanced MF stage had higher CCR4 expression. Conclusions CCR4 immunohistochemistry may be an adjunct in distinguishing advanced CD8+ MF from other CD8+ CTCLs/LPDs. Although CCR4 expression may justify therapeutic targeting of this receptor in CD8+ MF, the role of such therapies in other CD8+ CTCLs/LPDs is not yet clear.

A co‐expression network based molecular characterization of genes responsive for Braak stages in Parkinson's disease

“…There are some genes in the network that are not yet known to interact with SNCA protein, but they have co‐expression relations with SNCA‐interacting proteins (Figure 4). CCR4 is a C‐C chemokine receptor, and chemokines has an important role in the function of the immune system, development, homeostasis, and central nervous system development (Geller et al, 2020). In this network, CCR4 gene has interactions with two known SNCA‐interacting genes.…”

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas

“…The expression of the surface ligand CCR4 determines the T-cell skin homing ability, while CCR7/L-selectin controls their capacity to recirculate between the blood and lymph node. High CCR4 expression is consistently observed in advanced MF [1,32,35,36].…”

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

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