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

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.
Main Authors
Format
Articles Research article
Published
2021
Series
Subjects
Publication in research information system
Publisher
MDPI AG
The permanent address of the publication
https://urn.fi/URN:NBN:fi:jyu-202103312246Käytä tätä linkitykseen.
Review status
Peer reviewed
ISSN
2072-6694
DOI
https://doi.org/10.3390/cancers13071530
Language
English
Published in
Cancers
Citation
  • Ahtiainen, M., Elomaa, H., Väyrynen, J. P., Wirta, E.-V., Kuopio, T., Helminen, O., Seppälä, T. T., Kellokumpu, I., & Mecklin, J.-P. (2021). Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases. Cancers, 13(7), Article 1530. https://doi.org/10.3390/cancers13071530
License
CC BY 4.0Open Access
Additional information about 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© 2021 by the authors. Licensee MDPI, Basel, Switzerland

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