A1 Journal article (refereed)
Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases (2021)

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

JYU authors or editors

Publication details

All authors or editors: Ahtiainen, Maarit; Elomaa, Hanna; Väyrynen, Juha P.; Wirta, Erkki-Ville; Kuopio, Teijo; Helminen, Olli; Seppälä, Toni T.; Kellokumpu, Ilmo; Mecklin, Jukka-Pekka

Journal or series: Cancers

eISSN: 2072-6694

Publication year: 2021

Publication date: 26/03/2021

Volume: 13

Issue number: 7

Article number: 1530

Publisher: MDPI AG

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/cancers13071530

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/74914

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.

Keywords: bowel cancer; tumours; metastases; immune response; lymphocytes

Free keywords: colorectal cancer; metastases; tumour infiltrating lymphocytes

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2021

JUFO rating: 1