Cargando…

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study

Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD...

Descripción completa

Detalles Bibliográficos
Autores principales: Filoni, Angela, Cicco, Gerolamo, Cazzato, Gerardo, Bosco, Anna, Lospalluti, Lucia, Tucci, Marco, Cimmino, Antonietta, Foti, Caterina, Marzullo, Andrea, Bonamonte, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877121/
https://www.ncbi.nlm.nih.gov/pubmed/35207500
http://dx.doi.org/10.3390/life12020213
_version_ 1784658336094879744
author Filoni, Angela
Cicco, Gerolamo
Cazzato, Gerardo
Bosco, Anna
Lospalluti, Lucia
Tucci, Marco
Cimmino, Antonietta
Foti, Caterina
Marzullo, Andrea
Bonamonte, Domenico
author_facet Filoni, Angela
Cicco, Gerolamo
Cazzato, Gerardo
Bosco, Anna
Lospalluti, Lucia
Tucci, Marco
Cimmino, Antonietta
Foti, Caterina
Marzullo, Andrea
Bonamonte, Domenico
author_sort Filoni, Angela
collection PubMed
description Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. Objective: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. Methods: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student’s t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann–Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. Results: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. Conclusions: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can “open the doors” to development and eventual metastasis by this malignant neoplasm.
format Online
Article
Text
id pubmed-8877121
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88771212022-02-26 Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study Filoni, Angela Cicco, Gerolamo Cazzato, Gerardo Bosco, Anna Lospalluti, Lucia Tucci, Marco Cimmino, Antonietta Foti, Caterina Marzullo, Andrea Bonamonte, Domenico Life (Basel) Article Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. Objective: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. Methods: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student’s t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann–Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. Results: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. Conclusions: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can “open the doors” to development and eventual metastasis by this malignant neoplasm. MDPI 2022-01-30 /pmc/articles/PMC8877121/ /pubmed/35207500 http://dx.doi.org/10.3390/life12020213 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Filoni, Angela
Cicco, Gerolamo
Cazzato, Gerardo
Bosco, Anna
Lospalluti, Lucia
Tucci, Marco
Cimmino, Antonietta
Foti, Caterina
Marzullo, Andrea
Bonamonte, Domenico
Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title_full Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title_fullStr Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title_full_unstemmed Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title_short Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study
title_sort immune disregulation in cutaneous squamous cell carcinoma of patients with recessive dystrophic epidermolysis bullosa: a single pilot study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877121/
https://www.ncbi.nlm.nih.gov/pubmed/35207500
http://dx.doi.org/10.3390/life12020213
work_keys_str_mv AT filoniangela immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT ciccogerolamo immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT cazzatogerardo immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT boscoanna immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT lospallutilucia immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT tuccimarco immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT cimminoantonietta immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT foticaterina immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT marzulloandrea immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy
AT bonamontedomenico immunedisregulationincutaneoussquamouscellcarcinomaofpatientswithrecessivedystrophicepidermolysisbullosaasinglepilotstudy