Prognostic value of CD73 expression in resected colorectal cancer liver metastasis

Nouredin Messaoudi; Isabelle Cousineau; Elizabeth Arslanian; David Henault; David Stephen; Franck Vandenbroucke-Menu; Michel Dagenais; Richard Létourneau; Marylène Plasse; André Roy; Réal Lapointe; Dirk Ysebaert; Dominique Trudel; Geneviève Soucy; John Stagg; Simon Turcotte

doi:10.1080/2162402X.2020.1746138

Prognostic value of CD73 expression in resected colorectal cancer liver metastasis

Oncoimmunology. 2020 Apr 23;9(1):1746138. doi: 10.1080/2162402X.2020.1746138. eCollection 2020.

Authors

Nouredin Messaoudi^{1

2

3

4}, Isabelle Cousineau¹, Elizabeth Arslanian⁵, David Henault¹, David Stephen⁵, Franck Vandenbroucke-Menu², Michel Dagenais², Richard Létourneau², Marylène Plasse², André Roy², Réal Lapointe², Dirk Ysebaert³, Dominique Trudel^{1

5}, Geneviève Soucy⁵, John Stagg¹, Simon Turcotte^{1

2}

Affiliations

¹ Cancer Axis, Centre de Recherche Du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec, Canada.
² Hepatopancreatobiliary Surgery & Liver Transplantation Service, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.
³ Department of Surgery, University of Antwerp, Antwerp, Belgium.
⁴ Department of Surgery, University Hospital of Brussels (UZ Brussel) and Europe Hospitals, Brussels, Belgium.
⁵ Department of Pathology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada.

Abstract

Immune checkpoint blockade has not yet been effective in patients with mismatch repair proficient metastatic colorectal cancer. Targeting immunosuppressive metabolic pathways is being explored as a new immunotherapeutic approach. We assessed whether CD73, the rate limiting enzyme that catalyzes the degradation of extracellular AMP into immunosuppressive adenosine, could be an immunological determinant of colorectal liver metastases (CRLMs). By immunofluorescence on tissue microarrays, intratumoral CD73 expression (tCD73) was analyzed in 391 CRLMs resected in 215 patients, and soluble CD73 (sCD73) was measured by ELISA in the pre-operative serum of 193 patients. High tCD73 was associated with worse pathological features, such as multiple and larger CRLMs, and poorer pathologic response to pre-operative chemotherapy. The median time to recurrence and disease-specific survival after CRLM resection was significantly shorter in patients with high tCD73 (11.0 and 46.4 months, respectively) compared with low tCD73 (19.0 and 61.5 months, respectively). tCD73 was strongly associated with patient outcomes independently of clinicopathological variables. sCD73 did not correlate with tCD73. Patients with high levels of sCD73 also had shorter disease-specific survival. Our results suggested that CD73 in CRLMs may be prognostically informative and may help select patients more likely to respond to adenosine pathway blocking agents.

Keywords: CD73-Adenosine pathway; biomarker; colorectal cancer; immune checkpoint; liver metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Liver Neoplasms* / surgery
Neoplasm Recurrence, Local
Prognosis
Rectal Neoplasms*

Grants and funding

This work was supported by a research grant from Surface Oncology, who had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, by the Chaire Roger des Groseillers en oncologie chirurgicale hépatobiliaire et pancréatique de l’Université de Montréal, and start-up funding from Institut du cancer de Montréal, the CRCHUM, and the Université de Montréal Surgery Department. S.T. holds a Clinical Research Scholarship from the Fonds de recherche du Québec - Santé. N.M. was supported by the International Hepato-Pancreato-Biliary Association (IHPBA) Kenneth Warren Research Fellowship and Ethicon, Inc., a subsidiary of Johnson & Johnson. D.T. holds a Clinical Research Scholarship from the Fonds de recherche du Québec – Santé.