TY - JOUR
T1 - Prognostic value of CD73 expression in resected colorectal cancer liver metastasis
AU - Messaoudi, Nouredin
AU - Cousineau, Isabelle
AU - Arslanian, Elizabeth
AU - Henault, David
AU - Stephen, David
AU - Vandenbroucke-Menu, Franck
AU - Dagenais, Michel
AU - Létourneau, Richard
AU - Plasse, Marylène
AU - Roy, André
AU - Lapointe, Réal
AU - Ysebaert, Dirk
AU - Trudel, Dominique
AU - Soucy, Geneviève
AU - Stagg, John
AU - Turcotte, Simon
N1 - © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85084514018&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2020.1746138
DO - 10.1080/2162402X.2020.1746138
M3 - Article
C2 - 32363113
SN - 2162-4011
VL - 9
JO - Oncoimmunology
JF - Oncoimmunology
IS - 1
M1 - 1746138
ER -