University of Oulu

Ahtiainen, M., Elomaa, H., Väyrynen, J. P., Wirta, E.-V., Kuopio, T., Helminen, O., … Mecklin, J.-P. (2021). Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases. Cancers, 13(7), 1530. doi:10.3390/cancers13071530

Immune contexture of MMR-proficient primary colorectal cancer and matched liver and lung metastases

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Author: Ahtiainen, Maarit1; Elomaa, Hanna2; Väyrynen, Juha P.3,4;
Organizations: 1Department of Education and Research, Hospital Nova of Central Finland, 40620 Jyväskylä, Finland
2Department of Biological and Environmental Science, University of Jyväskylä, 40014 Jyväskylä, Finland
3Department of Pathology, Hospital Nova of Central Finland, 40620 Jyväskylä, Finland
4Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu
5Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33520 Tampere, Finland
6Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of Oulu, 90014 Oulu, Finland
7Department of Surgery, Hospital Nova of Central Finland, 40620 Jyväskylä, Finland
8Department of Surgery, Helsinki University Central Hospital, and University of Helsinki, 00014 Helsinki, Finland
9Surgical Oncology, Johns Hopkins University, Baltimore, MD 21218, USA
10iCAN Digital Precision Cancer Medicine Flagship, Helsinki University Central Hospital, and University of Helsinki, 00014 Helsinki, Finland
11Faculty of Sport and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021041910934
Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-04-19
Description:

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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Series: Cancers
ISSN: 2072-6694
ISSN-E: 2072-6694
ISSN-L: 2072-6694
Volume: 13
Issue: 7
Article number: 1530
DOI: 10.3390/cancers13071530
OADOI: https://oadoi.org/10.3390/cancers13071530
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Funding: T.T.S. was supported by research grants from Emil Aaltonen Foundation, Finnish Cancer Foundation, Finnish Medical Foundation, Sigrid Juselius Foundation, Instrumentarium Science Foundation and iCAN Flagship of the Academy of Finland. J.V. was supported by Finnish Cancer Foundation. O.H. was supported by State Research Fund, Mary and Georg. C. Ehrnrooth Foundation and Instrumentarium Science Foundation. J.-P.M. was supported by Finnish Cancer Foundation, Jane and Aatos Erkko Foundation and State Research Fund. Open access funding provided by University of Helsinki.
Copyright information: © 2021 by the authors. 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/).
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