A1 Journal article (refereed)
High immune cell infiltration predicts improved survival in cholangiocarcinoma (2024)


Wirta, E.-V., Szeto, S., Koppatz, H., Nordin, A., Mäkisalo, H., Arola, J., Sirén, J., Ahtiainen, M., Böhm, J., Mecklin, J.-P., Sallinen, V., & Seppälä, T. T. (2024). High immune cell infiltration predicts improved survival in cholangiocarcinoma. Frontiers in Oncology, 14, Article 1333926. https://doi.org/10.3389/fonc.2024.1333926


JYU authors or editors


Publication details

All authors or editors: Wirta, Erkki-Ville; Szeto, Säde; Koppatz, Hanna; Nordin, Arno; Mäkisalo, Heikki; Arola, Johanna; Sirén, Jukka; Ahtiainen, Maarit; Böhm, Jan; Mecklin, Jukka-Pekka; et al.

Journal or series: Frontiers in Oncology

eISSN: 2234-943X

Publication year: 2024

Publication date: 01/05/2024

Volume: 14

Article number: 1333926

Publisher: Frontiers Media

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3389/fonc.2024.1333926

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/94645


Abstract

Background: Antitumoral immune response has a crucial role in constraining cancer. However, previous studies on cholangiocarcinoma (CCA), a rare and aggressive cancer, have reported contradictory findings on the prognostic impact of tumor-infiltrating T-lymphocytes. We aimed to clarify the effect of tumor-infiltrating CD3+ and CD8+ lymphocytes and PD-1/PD-L1 expression on CCA prognosis.

Methods: CD3+, CD8+, and PD-1+ lymphocyte densities, as well as PD-L1 expression rate were analyzed from stained tissue microarray samples from the tumor center and invasive margin of 47 cholangiocarcinomas. The association of CD3+ and CD8+ based Immune cell score (ICS) and its components with overall survival was evaluated, adjusting for age, sex, TNM stage, radicality of surgery, tumor location, and PD-L1 expression on immune cells.

Results: Low ICS was a strong independent prognostic factor for worse overall survival (Hazard ratio 9.27, 95% confidence interval 2.72-31.64, P<0.001). Among the ICS components, high CD8+ lymphocyte infiltration at the tumor center had the most evident impact on patient outcome. PD-1 and PD-L1 expression on immune cells did not have a significant impact on overall survival alone; however, PD-L1 positivity seemed to impair survival for ICSlow subgroup.

Conclusion: Identifying patient subgroups that could benefit from immunotherapy with PD-1/PD-L1 pathway blockade may help improve treatment strategies for this aggressive cancer. Our findings highlight the importance of evaluating the immune contexture in cholangiocarcinoma, as ICS serves as a strong independent prognostic and selective factor for patients who might benefit from immunotherapy.


Keywords: cancerous diseases; digestive system diseases; cancer treatments; cancer cells; immune system; immunotherapy; lymphocytes; T-lymphocytes

Free keywords: cholangiocarcinoma; tumor-infiltrating T-lymphocytes; immune cell score; PD-1; PD-L1


Contributing organizations


Ministry reporting: Yes

Reporting Year: 2024

Preliminary JUFO rating: 1


Last updated on 2024-13-05 at 18:06