Related Experiment Video
Updated: Dec 22, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Prognostic value of CD73 expression in resected colorectal cancer liver metastasis
Nouredin Messaoudi1,2,3,4, Isabelle Cousineau1, Elizabeth Arslanian5
1Cancer Axis, Centre de Recherche Du Centre Hospitalier de l'Université de Montréal (CRCHUM), 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.
Insights
High intratumoral CD73 expression in colorectal liver metastases correlates with worse outcomes. This finding suggests CD73 may predict response to adenosine pathway inhibitors in cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Metabolic Pathways
Background:
- Immune checkpoint blockade is ineffective for mismatch repair proficient metastatic colorectal cancer.
- Targeting immunosuppressive metabolic pathways presents a novel immunotherapeutic strategy.
- CD73, an enzyme degrading extracellular AMP to adenosine, is a potential target.
Purpose of the Study:
- To investigate CD73 as an immunological determinant in colorectal liver metastases (CRLM).
- To correlate intratumoral CD73 (tCD73) and soluble CD73 (sCD73) with clinicopathological features and patient outcomes.
Main Methods:
- Immunofluorescence analysis of tCD73 on 391 CRLM tissue microarrays from 215 patients.
- ELISA measurement of sCD73 in pre-operative serum from 193 patients.
- Statistical analysis of associations between CD73 levels, pathological features, and survival.
Main Results:
- High tCD73 associated with worse pathological features (multiple/larger CRLMs, poorer chemotherapy response).
- High tCD73 significantly correlated with shorter time to recurrence and disease-specific survival.
- sCD73 levels did not correlate with tCD73 but high sCD73 also predicted shorter survival.
- tCD73 independently predicted patient outcomes.
Conclusions:
- CD73 in CRLMs is a significant prognostic marker.
- tCD73 levels can inform patient prognosis and selection for adenosine pathway blocking agents.
- Both intratumoral and soluble CD73 warrant further investigation in colorectal cancer treatment.
