Dendritic Cells and CD8+ Lymphocytes in Early Mycosis Fungoides.
Authors: Goteri Gaia , Filosa Alessandra , Rupoli Serena , Pulini Stefano , Tassetti Angela , Scortechini Anna Rita , Capretti Roberta , Stramazzotti Daniela , Mozzicafreddo Giorgio , Offidani Anna Maria , Morresi Lorenzo , Lanari Sergio , Fabris Guidalberto , Leoni Pietro 
Published: April 2020

Abstract
Dendritic cells (DCs) are immune accessory cells involved in the uptake, processing and presentation of antigens to reactive T cells. In Mycosis fungoides (MF), they are increased when compared to healthy skin, although their role has not yet been elucidated. The activation of the so called TILs (tumor infiltrating lymhocytes) is more efficient when DCs have completed their maturational process. Therefore, blockage of DCs maturation by MF neoplastic cells could represent a mechanism of tumoral escape.
The distribution and the density of DCs expressing CD207 (the langerin molecule) and CD1a, (the immature stage of their differentiation), together with the distribution and density of CD8 positive reactive lymphocytes (TILs), were analysed in MF skin lesions. Another purpose was to investigate the prognostic impact of langerin positive cells in terms of patients responsiveness to treatment and disease free survival (DFS).
33 MF patients (20 F, 13 M; mean age, 55.7 yrs, range 28–76) were included in the present study. 11 patients were in stage IA, 17 in stage IB, 4 in stage IIA and 1 in stage IIB. After treatment with PUVA and interferonα, 30 obtained a clinical complete remission, while 3 did not respond. After a mean follow-up of 29.3 months (range, 2–79), 8 patients relapsed, whereas 22 are still in complete remission. Immunostaining for langerin, CD1a, and CD8 was performed on skin formalin-fixed paraffin-embedded tissue sections obtained before the beginning of treatment and langerin, Cd1a and CD8 positive cell density was evaluated at light microscopy. Statistical analysis was performed using a SPPS statistical package.
Density of CD1a+ and langerin+epidermal DCs was, respectively, low in 6 and 11 cases, and high in 27 and 22. Density of CD1a+ and langerin+ dermal DCs was, respectively, low in 6 and 16 cases, and high in 27 and 17. Density of CD8+ lymphocytes was low in 8 and high in 25 cases. Density of dermal langerin+ DCs was more frequently high in cases with a band-like/nodular infiltrate (78.6%) than in cases with a not confluent infiltrate (31.6%; Fisher’s exact test: P=0.02).
Density of langerin+ epidermal DCs was low in all 3 cases in which therapy with PUVA and interferona did not achieve a complete remission (Fisher’s exact test: P=0.03). A shorter DFS was observed in patients with a low density of CD8+ lymphocytes (log rank test, P=0.03), and with a high density of both langerin+ dermal DCs (log rank test, P=0.005) and CD1a+ dermal DCs (log rank test, P=0.06): at 45 months all patients with a high density of langerin+ dermal DCs and a low density of CD8+ lymphocyte had the probability to relapse of 35% compared to 25% of those with a low density of langerin+ dermal DCs and a high density of CD8+ lymphocytes.
The presence of many epidermal langerin positive DCs appears to be an optimal base for a good clinical outcome in early MF with a combination of PUVA plus interferonα. A low number of CD8+ lymphocytes and many immature langerin+ dermal DCs seem to be related to an increased risk of disease relapse, and denote an unfavourable disease behaviour since MF neoplastic cells, by blocking dermal DCs maturation, may reduce TILs recruitment, thus impairing the anti-tumour immune response.