Mycosis fungoides and Sézary syndrome: Role of chemokines and chemokine receptors

Table 1 Role of chemokines and chemokines receptors in the pathogenesis of mycosis fungoides and Sézary syndrome[8,16,51-85]

Chemokine receptor	Chemokine	Role in pathogenesis of mycosis fungoides and Sézary syndrome
CCR4	CCL17 (TARC) CCL22	Increased percentages of T lymphocytes expressing CCR4 in the blood and skin lesions of CTCL patients Activation of CCR4 promoted migration of mycosis fungoides cell lines CCL17 expression is upregulated in the skin lesions and serum of mycosis fungoides patients
CCR10	CCL27 (CTACK)	CCR10 is expressed by malignant lymphocytes in skin lesions and peripheral blood of patients with mycosis fungoides and Sézary syndrome The level of CCL27 is increased in the serum and skin of patients with mycosis fungoides
CXCR4	CXCL12 (SDF)	CXCR4 is expressed by Sézary cells, and acts as a chemotactic factor for Sézary cells Loss of the cell-surface antigen CD26 (which cleaves and deactivates the CXCL12) is a characteristic feature in Sézary syndrome
CCR7	CCL19 (MIP-3b) CCL21 (SLC)	CCR7 is expressed on atypical lymphocytes of Sézary syndrome CCR7 promotes migration of Sézary cells CCR7 was expressed in mycosis fungoides skin lesions, and its expression correlated with subcutaneous extension of lymphoma cells Activation of CCR7 by its ligand CCL21 promotes MyLa (mycosis fungoides cell line) cell migration through the mTOR pathway
CCR3	Eotaxin-3 Eotaxin-1	Skin lesions of CTCL show higher expression of CCR3 and eotaxin-3 CTCL patients show higher serum levels of eotaxin-3 and eotaxin-1
CXCR3	CXCL9 CXCL10 CXCL11	CXCR3 is expressed in low-grade mycosis fungoides

CCR: CC chemokine receptor; CCL: Chemokine (C-C motif) ligand; TARC: Thymus and activation regulated chemokine; CTCL: Cutaneous T-cell lymphoma; CTACK: Cutaneous T-cell attracting chemokine; CXCR4: C-X-C chemokine receptor type 4; CXCL12: Chemokine (C-X-C Motif) ligand 12; SDF: Stromal cell-derived factor; MIP: Macrophage inflammatory protein; SLC: Secondary lymphoid-tissue chemokine.

Table 2 Current treatment strategies for mycosis fungoides and Sézary syndrome

Skin-directed therapies	Systemic therapies
Topical corticosteroids	Oral retinoid (bexarotene)
Topical nitrogen mustard	IL-12
Topical retinoid (bexarotene)	Interferon-α
Ultraviolet light phototherapy (PUVA, narrowband UVB)	Histone deacetylase inhibitors
	Extracorporeal photopheresis
Radiation therapy	Methotrexate
	Chemotherapy
	Hematopoietic stem cell transplantation

PUVA: Psoralen and ultraviolet-A; IL-12: Interleukin 12.