Prognostic Significance of B7-H3 Expression and CD163+ Tumor-Associated Macrophage Infiltration in Mesothelioma

Our plain-English summary of Prognostic Significance of B7-H3 Expression and CD163+ Tumor-Associated Macrophage Infiltration in Mesothelioma, by T. Koç, R.O. Yüceer, T. Altay, et al (International Journal of Molecular Sciences, 2026).

The study

• Authors: T. Koç, R.O. Yüceer, T. Altay, N. Taş, S. Çelikgün
• Journal: International Journal of Molecular Sciences
• Published: 2026;27(15)
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a rare, aggressive malignancy with poor prognosis. B7-H3 (CD276), an immune checkpoint molecule, and CD163-positive tumor-associated macrophages (TAMs) contribute to tumor progression and immune evasion. This study evaluated the prognostic impact of B7-H3 expression and CD163-positive TAM infiltration. This single-center retrospective study included 94 patients diagnosed with malignant mesothelioma between 2011 and 2024. B7-H3 expression was assessed using the H-score method and dichotomized at the cohort median. CD163-positive TAM density was quantified in hotspot high-power fields. Overall survival (OS) was analyzed using Kaplan-Meier, log-rank, and multivariable Cox regression analyses. Median OS was 10.15 months (IQR: 4.88-19.66). High B7-H3 expression was associated with shorter OS, whereas high CD163-positive TAM density was associated with longer OS. In multivariable analysis, B7-H3 expression, CD163 expression, tumor localization, recurrence status, and treatment status were independently associated with overall survival. Combined biomarker analysis showed the worst OS in the CD163-low/B7-H3-high group and the best OS in the CD163-high/B7-H3-low group. High B7-H3 expression was independently associated with shorter overall survival, whereas high CD163-positive TAM infiltration was associated with longer overall survival in this cohort. The combined B7-H3/CD163 profile may identify distinct prognostic subgroups and highlights the tumor immune microenvironment.

In plain English

This single-center retrospective study, from the pathology department of Sivas Cumhuriyet University in Turkey, examined tumor tissue from 94 patients diagnosed with malignant mesothelioma between 2011 and 2024. Of these, 72 had pleural and 22 had peritoneal mesothelioma. Asbestos exposure was identified in 80 patients (85.1%). The authors stained tumors for B7-H3, an immune checkpoint protein, and counted CD163-positive tumor-associated macrophages. They split patients into low and high groups at the cohort median for each marker. Median overall survival was 10.15 months. In the multivariable analysis, high B7-H3 was associated with a higher hazard of death (hazard ratio 1.85, 95% CI 1.06–3.23). High CD163 density was associated with a lower hazard (hazard ratio 0.40, 95% CI 0.23–0.69). Asbestos exposure was not significantly associated with survival in that analysis. The high-CD163/low-B7-H3 group (26 patients) had the longest mean survival, 26.49 months (95% CI 17.85–35.14). The low-CD163/high-B7-H3 group (13 patients) had the shortest, 6.30 months (95% CI 1.26–11.35). The authors called the CD163 finding unexpected and described the combined analysis as exploratory and hypothesis-generating.

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 archived pathology cases (immunohistochemistry and survival analysis)
• Who was studied: 94 patients diagnosed with malignant mesothelioma between 2011 and 2024 at Sivas Cumhuriyet University, Turkey: 72 (76.6%) pleural and 22 (23.4%) peritoneal; 56 male and 38 female; median age 66 years
• Exposure: The study's main factors were tumor B7-H3 expression (H-score, median cutoff 160) and CD163-positive macrophage density (median cutoff 45). A history of asbestos exposure was recorded as yes or no (80 yes, 14 no). No fiber types, sources or doses were reported.
• Main results:
  • Median overall survival for the whole cohort of 94 patients was 10.15 months (IQR 4.88–19.66).
  • In the multivariable Cox model, high B7-H3 expression (34 patients) was associated with a higher hazard of death compared with low expression: HR 1.85 (95% CI 1.06–3.23), p = 0.030.
  • In the multivariable model, high CD163 expression (47 patients) was associated with a lower risk of death compared with low expression. The text reports HR 0.405, p = 0.001; Table 4 reports HR 0.40 (95% CI 0.23–0.69), p less than 0.001.
  • Combined groups differed in survival (log-rank p less than 0.001). The CD163-high/B7-H3-low group (26 patients) had a mean overall survival of 26.49 months (95% CI 17.85–35.14) and a 5-year survival rate of 26.9%.
  • The CD163-low/B7-H3-high group (13 patients) had the poorest survival: mean overall survival 6.30 months (95% CI 1.26–11.35), with no patients alive at 5 years.
  • Asbestos exposure was not significantly associated with overall survival in the multivariable model. For no exposure versus exposure, HR was 1.08 (95% CI 0.53–2.19), p = 0.824. In the unadjusted comparison, mean survival was 15.20 months for exposed and 25.02 months for unexposed patients (p = 0.065).
  • In the multivariable model, patients with pleural tumors had a lower hazard of death than those with peritoneal tumors (adjusted HR 0.456, 95% CI 0.23–0.87, p = 0.019).
• The authors' conclusion: The authors concluded that, in this retrospective cohort, high B7-H3 expression was independently associated with shorter overall survival and high CD163-positive macrophage density with longer overall survival. They said these findings should be interpreted cautiously and that the combined analysis is exploratory and hypothesis-generating.
• Limitations the authors state:
  • Retrospective, single-center design and relatively small sample size limit external validity and raise the risk of selection bias and residual confounding.
  • The cohort mixed pleural and peritoneal mesothelioma, which the authors describe as distinct diseases. Site-specific analyses were not performed because the subgroups were very unequal in size.
  • Both markers were split at cohort-derived median values, and no independent validation cohort was available.
  • Only a limited set of stains was used. CD163 alone does not adequately define macrophage type, and markers such as CD68, CD8, CD20, FOXP3, PD-1 and PD-L1 were not evaluated.
  • Treatment data were incomplete and treatment was not randomized, so the treatment association should not be read as a causal treatment effect.
  • Only seven patients had recurrence, so the unexpected lower hazard of death in that group may be unstable or reflect survivorship bias.
  • Separate scores from each pathologist were not kept, so agreement between observers could not be measured.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Mesothelioma, Prognosis, High-Power Field, Overall Survival, Biomarker.

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• Expression status of PD-L1 and B7-H3 in mesothelioma — E. Matsumura, K. Kajino, et al. (2020)
• Expression and regulation of B7-H3 immunoregulatory receptor, in human mesothelial and mesothelioma cells: immunotherapeutic implications — L. Calabrò, L. Sigalotti, et al. (2011)
• Expression of V-set immunoregulatory receptor in malignant mesothelioma — Y.S. Chung, M. Kim, et al. (2020)
• New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma — N. Joalland, A. Quéméner, et al. (2025)

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