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Tolerogenic IDO1CD83 Langerhans Cells in Sentinel Lymph Nodes of Patients with Melanoma. | LitMetric

Tolerogenic IDO1CD83 Langerhans Cells in Sentinel Lymph Nodes of Patients with Melanoma.

Int J Mol Sci

Plastic and Reconstructive Surgery Unit, Regional Melanoma Referral Center and Melanoma & Skin Cancer Unit, Santa Maria Annunziata Hospital, 50012 Florence, Italy.

Published: March 2022

AI Article Synopsis

  • Langerhans cells (LCs) play a significant role in regulating immune responses against cancer, but their functions can be altered by cancer itself, leading to immune tolerance.
  • In melanoma patients, research reveals that certain LCs in sentinel lymph nodes express the enzyme indoleamine 2,3-dioxygenase (IDO1) and show signs of altered functionality.
  • The study identifies different subsets of LCs based on IDO1 and CD83 expression, finding that a specific subset linked to immune tolerance increases in metastatic sentinel lymph nodes and in those with a higher mitotic rate in melanoma.

Article Abstract

Langerhans cells (LCs) are crucial regulators of anti-cancer immune responses. Cancer, however, can alter DCs functions leading to tolerance. The enzyme indoleamine 2,3-dioxygenase (IDO1) plays a crucial role in this process. In sentinel lymph nodes (SLNs) of patients with melanoma, LCs show phenotypical and functional alterations favoring tolerance. Herein we aimed to investigate IDO1 expression in SLN LCs from patients with melanoma. We showed by immunofluorescence analysis that a portion of Langerin+ LCs, located in the SLN T cell-rich area, displayed the typical dendritic morphology and expressed IDO1. There was no significant difference in the expression of IDO between SLN with or without metastases. Double IDO1/CD83 staining identified four LCs subsets: real mature IDO1−CD83+ LCs; real immature IDO1−CD83− LCs; tolerogenic mature IDO1+CD83+ LCs; tolerogenic immature IDO1+CD83− LCs. The latter subset was significantly increased in metastatic SLNs as compared to negative ones (p < 0.05), and in SLN LCs of patients with mitotic rate (MR) > 1 in primary melanoma, as compared to MR ≤ 1 (p < 0.05). Finally, immature SLN LCs, after in vitro stimulation by inflammatory cytokines, acquired a maturation profile by CD83 up-regulation. These results provide new input for immunotherapeutic approaches targeting in vivo LC of patients with melanoma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998685PMC
http://dx.doi.org/10.3390/ijms23073441DOI Listing

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