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PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma

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Abstract

Cholangiocarcinoma, the second most common liver malignancy, after hepatocarcinoma is highly aggressive and usually diagnosed in advanced cases. In the era of personalized medicine, targeted therapy protocols are limited for cholangiocarcinoma and the only potential curative treatment, surgical resection, is seldom applicable.

This retrospective study included all cases with pathology-confirmed intrahepatic cholangiocarcinoma admitted in a tertiary healthcare facility during a 10-year timeframe. Clinical information, laboratory values, imaging studies, and survival data were retrieved, and PD-L1 immunostaining was performed on representative pathology slides, for each case.

From the total of 136 included cases (49 surgical resections and 87 liver biopsies), 38.97% showed PD-L1 positivity on tumoral cells, 34.8% on tumor infiltrating immune cells, 10.11% on epithelial cells within the peritumoral area and 15.95% on immune cells from the peritumoral area. Overall survival was significantly higher in the first two scenarios. However, after adjusting for age, tumor number, tumor size, and tumor differentiation in a multivariate analysis, only PD-L1 positivity on tumor infiltrating immune cells remained a favorable prognostic for survival. High immune cell counts also correlated with increased overall survival.

Our study demonstrated that PD-1/PD-L1 checkpoint pathway in the microenvironment of intrahepatic cholangiocarcinoma bears prognostic significance. PD-L1 expression on immune cells, in both resection and biopsy specimens, might be a strong independent predictor for a favorable outcome.

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Abbreviations

CCA:

Cholangiocarcinoma

iCCA:

Intrahepatic cholangiocarcinoma

OS:

Overall survival

PD-1:

Programmed cell death 1

PD-L1:

Programmed cell death ligand 1

TIF:

Tumor invasion front

TILs:

Tumor infiltrating lymphocytes

TME :

Tumor microenvironment

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Funding

Funding was provided by Universitatea de Medicină şi Farmacie Iuliu Haţieganu Cluj-Napoca (Grant No. 1530/58/18.01.2019).

Author information

Authors and Affiliations

  1. Department of Histology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Lavinia Patricia Mocan, Carmen Stanca Melincovici & Carmen Mihaela Mihu

  2. 3rd Medical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Rares Craciun & Zeno Sparchez

  3. Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Cristiana Grapa

  4. 3rd Pathology Department, Institute for Gastroenterology and Hepatology, Cluj-Napoca, Romania

    Ioana Rusu

  5. 3rd Surgical Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Nadim Al Hajjar

  6. Department of Medical Informatics and Biostatistics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Daniel Leucuta

  7. Department of Proteomics and Metabolomics, MedFUTURE Research Center for Advanced Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Maria Ilies

  8. 2nd Pediatrics Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Mihaela Sparchez

  9. Department of Gastroenterology, “Octavian Fodor” Institute for Gastroenterology and Hepatology, Cluj-Napoca, Romania

    Tudor Mocan

Authors
  1. Lavinia Patricia Mocan
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  2. Rares Craciun
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  9. Maria Ilies
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  12. Carmen Mihaela Mihu
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Contributions

L.P.M., T.M., M.I., C.M.M. developed the concept of the study. L.P.M., Z.S., N.H., I.R. gathered the database. L.P.M., C.S.M, I.R. performed pathologic assessments. D.L., T.M., M.S., M.I, performed the statistical analysis, interpreted and sketched the results. L.P.M., R.C., C.G., T.M. drafted the manuscript. T.M, Z.S., N.H., C.M.M. supervised the findings and provided feedback for the article. All authors discussed the results and reviewed the manuscript.

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Correspondence to Tudor Mocan.

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Mocan, L.P., Craciun, R., Grapa, C. et al. PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for patients with intrahepatic cholangiocarcinoma. Cancer Immunol Immunother 72, 1003–1014 (2023). https://doi.org/10.1007/s00262-022-03309-y

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