Immune Contexture of MMR-Proficient Primary Colorectal Cancer and Matched Liver and Lung Metastases
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
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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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Additional information about fundingT.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 ...
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