Jacqueline Wyss1, Bastian Dislich2, Viktor H Koelzer3, José A Galván2, Heather Dawson2, Marion Hädrich4, Daniel Inderbitzin5, Alessandro Lugli2, Inti Zlobec2, Martin D Berger6. 1. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland. 2. Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland. 3. Division of Clinical Pathology, Institute of Pathology, University of Bern, Bern, Switzerland; Molecular and Population Genetics Laboratory, University of Oxford, Oxford, UK. 4. Departments of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 5. Departments of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department of Surgery, Bürgerspital Solothurn, Solothurn, Switzerland. 6. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: martin.berger@insel.ch.
Abstract
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.
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 cancerpatients. 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 cancerpatients. 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 cancerpatients, 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 cancerpatients.
Authors: Megan M Harper; Miranda Lin; Michael J Cavnar; Prakash K Pandalai; Reema A Patel; Mei Gao; Joseph Kim Journal: PLoS One Date: 2022-07-07 Impact factor: 3.752
Authors: Lei Sun; Árpád V Patai; Tara L Hogenson; Martin E Fernandez-Zapico; Bo Qin; Frank A Sinicrope Journal: Oncogene Date: 2021-06-30 Impact factor: 9.867
Authors: Phillip M Kemp Bohan; Robert C Chick; Annelies T Hickerson; Lynn M Messersmith; Grant M Williams; Jessica L Cindass; Jamie Lombardo; Ryan Collins; Robert O Brady; Diane F Hale; George E Peoples; Timothy J Vreeland; Guy T Clifton Journal: Cancer Immunol Immunother Date: 2020-11-12 Impact factor: 6.630