Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases

SIMPLE SUMMARY: Metastasis is the main cause for cancer mortality. The most common metastatic sites of colorectal cancer (CRC) are the liver and lungs. Tumour-infiltrating lymphocytes are recognized as beneficial prognostic factors both in primary and metastatic CRC, but less is known about their re...

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Autores principales: Ahtiainen, Maarit, Elomaa, Hanna, Väyrynen, Juha P., Wirta, Erkki-Ville, Kuopio, Teijo, Helminen, Olli, Seppälä, Toni T., Kellokumpu, Ilmo, Mecklin, Jukka-Pekka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037224/
https://www.ncbi.nlm.nih.gov/pubmed/33810354
http://dx.doi.org/10.3390/cancers13071530
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author Ahtiainen, Maarit
Elomaa, Hanna
Väyrynen, Juha P.
Wirta, Erkki-Ville
Kuopio, Teijo
Helminen, Olli
Seppälä, Toni T.
Kellokumpu, Ilmo
Mecklin, Jukka-Pekka
author_facet Ahtiainen, Maarit
Elomaa, Hanna
Väyrynen, Juha P.
Wirta, Erkki-Ville
Kuopio, Teijo
Helminen, Olli
Seppälä, Toni T.
Kellokumpu, Ilmo
Mecklin, Jukka-Pekka
author_sort Ahtiainen, Maarit
collection PubMed
description SIMPLE SUMMARY: Metastasis is the main cause for cancer mortality. The most common metastatic sites of colorectal cancer (CRC) are the liver and lungs. Tumour-infiltrating lymphocytes are recognized as beneficial prognostic factors both in primary and metastatic CRC, but less is known about their reciprocal differences. The aim of our study was to evaluate immune microenvironment and its prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. The proportion of tumours with high immune cell infiltration together with PD-L1-positivity almost doubled in metastases compared to primary tumours. Our study confirmed the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC. ABSTRACT: Purpose: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 from 113 primary CRC tumours with 105 liver and 59 lung metastases were analyzed. The amount of CD3 and CD8 positive lymphocytes were combined as immune cell score (ICS). Comparative analyses on immune contexture were performed both between the primary tumour and matched metastases and between the metastatic sites. Results: In liver metastases, immune cell infiltration was increased in general compared to primary tumours but did not correlate case by case. On the contrary, ICS between lung metastases and primary tumours correlated well, but the expression of PD-1/PD-L1 was increased in lung metastases. The proportion of tumours with high ICS together with PD-L1-positivity almost doubled in metastases (39%) compared to primary tumours (20%). High ICS (compared to lowest) in patient’s least immune-infiltrated metastasis was an independent prognostic marker for disease-specific (HR 9.14, 95%CI 2.81–29.68) and overall survival (HR 6.95, 95%CI 2.30–21.00). Conclusions: Our study confirms the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC.
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spelling pubmed-80372242021-04-12 Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases Ahtiainen, Maarit Elomaa, Hanna Väyrynen, Juha P. Wirta, Erkki-Ville Kuopio, Teijo Helminen, Olli Seppälä, Toni T. Kellokumpu, Ilmo Mecklin, Jukka-Pekka Cancers (Basel) Article SIMPLE SUMMARY: Metastasis is the main cause for cancer mortality. The most common metastatic sites of colorectal cancer (CRC) are the liver and lungs. Tumour-infiltrating lymphocytes are recognized as beneficial prognostic factors both in primary and metastatic CRC, but less is known about their reciprocal differences. The aim of our study was to evaluate immune microenvironment and its prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. The proportion of tumours with high immune cell infiltration together with PD-L1-positivity almost doubled in metastases compared to primary tumours. Our study confirmed the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC. ABSTRACT: Purpose: To evaluate immune cell infiltration, the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) expression and their prognostic value in a series of mismatch proficient (pMMR) CRC with matched liver and lung metastases. Methods: Formalin-fixed paraffin-embedded tissue sections stained for CD3, CD8, PD-L1 and PD-1 from 113 primary CRC tumours with 105 liver and 59 lung metastases were analyzed. The amount of CD3 and CD8 positive lymphocytes were combined as immune cell score (ICS). Comparative analyses on immune contexture were performed both between the primary tumour and matched metastases and between the metastatic sites. Results: In liver metastases, immune cell infiltration was increased in general compared to primary tumours but did not correlate case by case. On the contrary, ICS between lung metastases and primary tumours correlated well, but the expression of PD-1/PD-L1 was increased in lung metastases. The proportion of tumours with high ICS together with PD-L1-positivity almost doubled in metastases (39%) compared to primary tumours (20%). High ICS (compared to lowest) in patient’s least immune-infiltrated metastasis was an independent prognostic marker for disease-specific (HR 9.14, 95%CI 2.81–29.68) and overall survival (HR 6.95, 95%CI 2.30–21.00). Conclusions: Our study confirms the prognostic value of high ICS in least immune-infiltrated metastases in pMMR CRC patients. Major differences observed in immune contexture between primary tumours and metastases may have significance for treatment strategies for patients with advanced CRC. MDPI 2021-03-26 /pmc/articles/PMC8037224/ /pubmed/33810354 http://dx.doi.org/10.3390/cancers13071530 Text en © 2021 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 (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Ahtiainen, Maarit
Elomaa, Hanna
Väyrynen, Juha P.
Wirta, Erkki-Ville
Kuopio, Teijo
Helminen, Olli
Seppälä, Toni T.
Kellokumpu, Ilmo
Mecklin, Jukka-Pekka
Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title_full Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title_fullStr Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title_full_unstemmed Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title_short Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
title_sort immune contexture of mmr-proficient primary colorectal cancer and matched liver and lung metastases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037224/
https://www.ncbi.nlm.nih.gov/pubmed/33810354
http://dx.doi.org/10.3390/cancers13071530
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