Impact of CD73/CD155 Expression on Survival in Resected Epithelial Pleural Mesothelioma: A Retrospective Single-center Study

Our plain-English summary of Impact of CD73/CD155 Expression on Survival in Resected Epithelial Pleural Mesothelioma: A Retrospective Single-center Study, by Y. Nabe, Y. Fujita, T. Hashimoto, et al (In Vivo, 2026).

The study

• Authors: Y. Nabe, Y. Fujita, T. Hashimoto, K. Tanaka, T. Manabe, K. Yoshimatsu, Y. Nemoto, N. Nishizawa, R. Oyama, Y. Honda, M. Mori, H. Matsumiya, M. Kanayama, A. Taira, M. Takenaka, K. Kuroda, S. Shimajiri, F. Tanaka
• Journal: In Vivo
• Published: 2026;40(4):2204-2224
• Read it: PubMed · Publisher · Free full text

Abstract

Background/aim: While CD73 and CD155 are implicated in immune evasion and tumor progression, their roles in pleural mesothelioma (PM) remain unclear. Therefore, we investigated the association between CD73 and CD155 expression in resected epithelial PM specimens and explored their impact on 5-year progression-free survival (PFS) and 5-year overall survival (OS).

Patients And Methods: This single-center retrospective study enrolled 43 patients with epithelial PM who underwent curative-intent surgery, with/without chemotherapy and immune checkpoint inhibitor (ICI) treatment, between January 2013 and December 2020. HALO-AI pathology software was used to quantify CD73 and CD155 expression following immunohistochemical staining. Cutoff values for CD73/CD155 positivity were determined using receiver operating characteristic curves. Patients were categorized into CD73+/CD155+ and non-CD73+/CD155+ groups, and survival outcomes were analyzed using Kaplan-Meier curves and Cox proportional hazards regression.

Results: Among 35 cases, patients with CD73+/CD155+ tumors exhibited significantly improved 5-year PFS compared with those with non-CD73+/CD155+ tumors (64.8% vs. 10.8%, p=0.017); however, OS differences were not significant (p=0.376). Among CD73+/CD155+ cases, postoperative pleurodesis with OK432 was associated with improved PFS (83.3% vs. 33.3%, p=0.03). Among non-CD73+/CD155+ cases, postoperative chemotherapy significantly improved PFS (p<0.001). Univariate analysis identified non-CD73+/CD155+ expression as an independent predictor of disease progression [hazard ratio (HR)=0.2546, p=0.02933]. Among recurrent cases, patients treated with ICIs exhibited significantly improved OS (p=0.001), highlighting the potential of immunotherapy.

Conclusion: CD155 may serve as a poor prognostic factor in mesothelioma and represents the first immunohistochemical evaluation of this marker. Although CD73 and CD155 co-expression were initially predicted to indicate poor prognosis, findings were unexpected, likely due to inability to establish an optimal cutoff value given variations in patient demographics, disease stage, and treatment approaches.

Copyright © 2026, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

In plain English

This single-center retrospective study from Japan examined tumor tissue from patients with epithelial pleural mesothelioma who had surgery between 2013 and 2020. It did not examine asbestos exposure. Of 43 consecutive patients included, results were reported for 35. Using AI-assisted image analysis, the authors measured the percentage of tumor cells carrying two proteins, CD73 and CD155, and classed 10 patients as positive for both. Contrary to the authors' expectation, these 10 had better 5-year progression-free survival than the other 25 (64.8% vs 10.8%, p=0.017). The difference in 5-year overall survival (55.6% vs 27.9%) was not statistically significant (p=0.376). In an additional analysis, a higher percentage of CD155-positive cells was associated with a higher risk of death (hazard ratio 1.1450, 95% CI 1.0150 to 1.292). Among 24 patients whose disease recurred, those who received chemotherapy with a history of immune checkpoint inhibitor treatment had significantly better survival (p=0.001). The authors concluded that CD155 may be a poor prognostic factor needing further research. They noted that the small sample gave a statistical power of 59.6%.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center retrospective study of surgically resected tumor specimens, with immunohistochemistry measured by AI-based image analysis
• Who was studied: Patients with epithelial pleural mesothelioma who had surgery at the University of Occupational and Environmental Health, Japan, from January 1, 2013, to December 31, 2020. 43 consecutive patients were included and 35 were analyzed (30 men, 5 women). Patients who did not consent or whose progression dates were unknown were excluded.
• Exposure: No asbestos exposure was studied. The factor examined was the percentage of tumor cells positive for the proteins CD73 and CD155 in resected tumor tissue, measured with HALO-AI software. Postoperative treatments (pleurodesis with OK432, chemotherapy, immune checkpoint inhibitors) were also compared.
• Main results:
  • Cutoffs for positivity, set by ROC curve analysis, were at least 8.63% of cells for CD73 and at least 3.75% for CD155. 10 of 35 patients (28.6%) were CD73+/CD155+ and 25 (71.4%) were not.
  • 5-year progression-free survival was 64.8% in the CD73+/CD155+ group versus 10.8% in the other groups (p=0.017).
  • 5-year overall survival was 55.6% in the CD73+/CD155+ group and 27.9% in the non-CD73+/CD155+ group. The difference was not statistically significant (p=0.376).
  • In univariate Cox analysis of progression-free survival, CD73+/CD155+ status (yes vs. no) had a hazard ratio of 0.2546 (95% CI 0.0744 to 0.8715, p=0.02933), meaning a decreased risk of disease progression.
  • In univariate analysis of overall survival, postoperative pleurodesis (HR=0.2826, 95% CI 0.106 to 0.7535, p=0.01155) and postoperative chemotherapy (HR=0.2857, 95% CI 0.107 to 0.7627, p=0.01239) were associated with a reduced risk of death. CD73+/CD155+ status was not significant (HR 0.61, 95% CI 0.2 to 1.861, p=0.385).
  • In the CD73+/CD155+ group, patients who had postoperative pleurodesis with OK432 tended to have better progression-free survival than those who did not (83.3% vs. 33.3%, p=0.03).
  • In the non-CD73+/CD155+ group, 5-year progression-free survival was 12.9% with postoperative chemotherapy and 0% without. In the CD73+/CD155+ group it was 66.7% regardless of chemotherapy.
  • Among the 24 patients with recurrence, the group that received chemotherapy with a history of immune checkpoint inhibitor treatment had significantly better 5-year overall survival than the groups with no chemotherapy or with chemotherapy without ICI use (p=0.001).
  • In the multivariate analysis of overall survival, a higher percentage of CD155-positive tumor cells was associated with an increased risk of death (HR=1.1450, 95% CI 1.0150 to 1.292, p=0.02717). In the univariate analysis the HR was 1.079 (95% CI 1.009 to 1.155, p=0.02742). The percentage of CD73-positive cells was not significant.
• The authors' conclusion: The authors stated that their results were contrary to their expectation that CD73-positive and CD155-positive patients would do worse. They attributed this to the inability to set an effective cutoff for CD155, given variations in patient sex, disease stage and treatment. They concluded that CD155 may be a poor prognostic factor for mesothelioma, warranting further research.
• Limitations the authors state:
  • Because the study was retrospective, some patients were followed up at other hospitals after surgery, which led to missing data.
  • The study was at a single institution with only 35 patients. This was below the required sample size, giving a statistical power of 59.6%.
  • The use of multidisciplinary treatment introduced potential bias in progression-free survival.
  • The AI analysis functions as a 'black box'. Only one pathologist reviewed the slides, so the study may lack objectivity.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Progression-Free Survival, Overall Survival, Chemotherapy, checkpoint inhibitors, Pathology, Immunohistochemistry, Kaplan-Meier Curve.

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