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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8997641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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