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

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http://hdl.handle.net/10138/330816

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Ahtiainen , M , Elomaa , H , Vayrynen , J P , Wirta , E-V , Kuopio , T , Helminen , O , Seppala , T T , Kellokumpu , I & Mecklin , J-P 2021 , ' Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases ' , Cancers , vol. 13 , no. 7 , 1530 . https://doi.org/10.3390/cancers13071530

Title: Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
Author: Ahtiainen, Maarit; Elomaa, Hanna; Vayrynen, Juha P.; Wirta, Erkki-Ville; Kuopio, Teijo; Helminen, Olli; Seppala, Toni T.; Kellokumpu, Ilmo; Mecklin, Jukka-Pekka
Contributor organization: HUS Abdominal Center
Clinicum
University of Helsinki
Department of Surgery
Digital Precision Cancer Medicine (iCAN)
Helsinki University Hospital Area
Date: 2021-04
Language: eng
Number of pages: 16
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers13071530
URI: http://hdl.handle.net/10138/330816
Abstract: 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. 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.
Subject: colorectal cancer
metastases
tumour infiltrating lymphocytes
PD-1
PD-L1
3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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