Stromal PD-1/PD-L1 Expression Predicts Outcome in Colon Cancer Patients.

Wyss, Jacqueline; Dislich, Bastian; Kölzer, Viktor; Galván, José A.; Dawson, Heather; Hädrich, Marion; Inderbitzin, Daniel; Lugli, Alessandro; Zlobec, Inti; Berger, Martin D. (2019). Stromal PD-1/PD-L1 Expression Predicts Outcome in Colon Cancer Patients. Clinical colorectal cancer, 18(1), e20-e38. Elsevier 10.1016/j.clcc.2018.09.007

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INTRODUCTION The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host's antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to evaluate the differential impact of stromal and epithelial PD-L1 expression of primary tumors and liver metastasis on overall survival (OS) in colon cancer patients. PATIENTS AND METHODS Using a next-generation tissue microarray approach, we assessed both epithelial and stromal PD-L1 expression levels in primary tumors (n = 279) and corresponding liver metastases (n = 14) of colon cancer patients. PD-L1 positivity was graded according to the percentage (0.1%-1%, > 1%, > 5%, > 50%) of tumor cells with membranous PD-L1 expression or as the percentage of positive stroma cells and associated inflammatory infiltrates. We also assessed the interplay between stromal PD-1/PD-L1 and both intratumoral and stromal CD8 count and their impact on outcome. The primary end point was OS. RESULTS Stromal PD-L1 and PD-1 expression were both associated with less aggressive tumor behavior in colon cancer patients, which translated into better OS and disease-free survival, respectively. Conversely, PD-L1 staining in the tumor cells was less frequent than stromal staining and was associated with features of aggressive tumor biology, although without impact on outcome. Interestingly, the PD-L1 staining pattern remained similar between primary tumors and corresponding liver metastases. Stromal PD-1 expression correlated significantly with stromal PD-L1 staining and both intratumoral and stromal CD8 expression. CONCLUSION Stromal PD-1/PD-L1 expression might serve as a prognostic marker in colon cancer patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine

UniBE Contributor:

Dislich, Bastian; Kölzer, Viktor; Galván Hernández, José Alberto; Dawson, Heather; Hädrich, Marion; Lugli, Alessandro; Zlobec, Inti and Berger, Martin Dave

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1938-0674

Publisher:

Elsevier

Language:

English

Submitter:

Alessandro Lugli

Date Deposited:

03 Dec 2018 11:06

Last Modified:

27 Mar 2019 01:31

Publisher DOI:

10.1016/j.clcc.2018.09.007

PubMed ID:

30389315

Uncontrolled Keywords:

Biomarker CD8 expression Immune checkpoints Immunohistochemistry Survival

BORIS DOI:

10.7892/boris.121734

URI:

https://boris.unibe.ch/id/eprint/121734

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