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Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer

SIMPLE SUMMARY: Cancer cells escape macrophage phagocytosis by exploiting the CD47/SIRPα axis. We found that extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score was linked with i...

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Autores principales: Giatromanolaki, Alexandra, Mitrakas, Achilleas, Anestopoulos, Ioannis, Kontosis, Andreas, Koukourakis, Ioannis M., Pappa, Aglaia, Panayiotidis, Mihalis I., Koukourakis, Michael I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997641/
https://www.ncbi.nlm.nih.gov/pubmed/35406573
http://dx.doi.org/10.3390/cancers14071801
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author Giatromanolaki, Alexandra
Mitrakas, Achilleas
Anestopoulos, Ioannis
Kontosis, Andreas
Koukourakis, Ioannis M.
Pappa, Aglaia
Panayiotidis, Mihalis I.
Koukourakis, Michael I.
author_facet Giatromanolaki, Alexandra
Mitrakas, Achilleas
Anestopoulos, Ioannis
Kontosis, Andreas
Koukourakis, Ioannis M.
Pappa, Aglaia
Panayiotidis, Mihalis I.
Koukourakis, Michael I.
author_sort Giatromanolaki, Alexandra
collection PubMed
description SIMPLE SUMMARY: Cancer cells escape macrophage phagocytosis by exploiting the CD47/SIRPα axis. We found that extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score was linked with improved overall survival. High expression, however, of SIRPα by CD68+ TAMs was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis. A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs was also noted. The CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC. ABSTRACT: Background: Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRPα ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development. Methods: We investigated the expression of CD47/SIRPα molecules in a series of 98 NSCLCs, in parallel with the infiltration of tumor stroma by CD68+ macrophages, tumor-infiltrating lymphocytes (TILs), and PD-L1/PD-1 molecules. Results: Extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed, to a varying extent, by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score in inner tumor areas was linked with improved overall survival (p = 0.005); and this was independent of the stage (p = 0.02, hazard ratio 0.4). In contrast, high SIRPα expression by CD68+ TAMs (SIRPα/CD68-ratio) was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis (p = 0.02). A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs (p = 0.01, r = 0.25) was also noted. Conclusions: TAMs play an important role in the prognosis of operable NSCLC. As SIRPα+ macrophages adversely affect prognosis, it is suggested that the CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC.
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spelling pubmed-89976412022-04-12 Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer Giatromanolaki, Alexandra Mitrakas, Achilleas Anestopoulos, Ioannis Kontosis, Andreas Koukourakis, Ioannis M. Pappa, Aglaia Panayiotidis, Mihalis I. Koukourakis, Michael I. Cancers (Basel) Article SIMPLE SUMMARY: Cancer cells escape macrophage phagocytosis by exploiting the CD47/SIRPα axis. We found that extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score was linked with improved overall survival. High expression, however, of SIRPα by CD68+ TAMs was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis. A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs was also noted. The CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC. ABSTRACT: Background: Cancer cells escape macrophage phagocytosis by expressing the CD47 integrin-associated protein that binds to the SIRPα ligand (signal regulatory protein alpha) expressed by macrophages. Immunotherapy targeting this pathway is under clinical development. Methods: We investigated the expression of CD47/SIRPα molecules in a series of 98 NSCLCs, in parallel with the infiltration of tumor stroma by CD68+ macrophages, tumor-infiltrating lymphocytes (TILs), and PD-L1/PD-1 molecules. Results: Extensive membranous CD47 expression by cancer cells characterized 29/98 cases. SIRPα and CD68 were expressed, to a varying extent, by tumor-associated macrophages (Μφ, TAMs). A high CD68Mφ-score in inner tumor areas was linked with improved overall survival (p = 0.005); and this was independent of the stage (p = 0.02, hazard ratio 0.4). In contrast, high SIRPα expression by CD68+ TAMs (SIRPα/CD68-ratio) was linked with CD47 expression by cancer cells, low TIL-score, and poor prognosis (p = 0.02). A direct association of CD47 expression by cancer cells and the % FOXP3+ TILs (p = 0.01, r = 0.25) was also noted. Conclusions: TAMs play an important role in the prognosis of operable NSCLC. As SIRPα+ macrophages adversely affect prognosis, it is suggested that the CD47/SIRPα axis is a sound target for adjuvant immunotherapy policies, aiming to improve the cure rates in operable NSCLC. MDPI 2022-04-01 /pmc/articles/PMC8997641/ /pubmed/35406573 http://dx.doi.org/10.3390/cancers14071801 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
Giatromanolaki, Alexandra
Mitrakas, Achilleas
Anestopoulos, Ioannis
Kontosis, Andreas
Koukourakis, Ioannis M.
Pappa, Aglaia
Panayiotidis, Mihalis I.
Koukourakis, Michael I.
Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title_full Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title_fullStr Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title_full_unstemmed Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title_short Expression of CD47 and SIRPα Macrophage Immune-Checkpoint Pathway in Non-Small-Cell Lung Cancer
title_sort expression of cd47 and sirpα macrophage immune-checkpoint pathway in non-small-cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8997641/
https://www.ncbi.nlm.nih.gov/pubmed/35406573
http://dx.doi.org/10.3390/cancers14071801
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