TY - JOUR
T1 - High immune cell infiltration predicts improved survival in cholangiocarcinoma
AU - Wirta, Erkki Ville
AU - Szeto, Säde
AU - Koppatz, Hanna
AU - Nordin, Arno
AU - Mäkisalo, Heikki
AU - Arola, Johanna
AU - Sirén, Jukka
AU - Ahtiainen, Maarit
AU - Böhm, Jan
AU - Mecklin, Jukka Pekka
AU - Sallinen, Ville
AU - Seppälä, Toni T.
N1 - Publisher Copyright:
Copyright © 2024 Wirta, Szeto, Koppatz, Nordin, Mäkisalo, Arola, Sirén, Ahtiainen, Böhm, Mecklin, Sallinen and Seppälä.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - cholangiocarcinoma
KW - immune cell score
KW - PD-1
KW - PD-L1
KW - tumor-infiltrating T-lymphocytes
U2 - 10.3389/fonc.2024.1333926
DO - 10.3389/fonc.2024.1333926
M3 - Article
AN - SCOPUS:85193275256
SN - 2234-943X
VL - 14
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1333926
ER -