Prognostic Significance of Tumor-Cell VISTA Expression on Survival Outcomes in Nivolumab-Treated Pleural Mesothelioma: The HOT1901 Retrospective Multi-Institutional Study

Our plain-English summary of Prognostic Significance of Tumor-Cell VISTA Expression on Survival Outcomes in Nivolumab-Treated Pleural Mesothelioma: The HOT1901 Retrospective Multi-Institutional Study, by H. Yokouchi, H. Nishihara, Y. Kenmotsu, et al (ImmunoTargets and Therapy, 2026).

The study

• Authors: H. Yokouchi, H. Nishihara, Y. Kenmotsu, K. Tsuji, T. Kishikawa, H. Kikuchi, E. Miyauchi, Y. Nagano, K. Kanazawa, J. Sugisaka, T. Ohkuri, S. Oizumi
• Journal: ImmunoTargets and Therapy
• Published: 2026;15:585001
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Nivolumab is used as a second-line treatment for pleural mesothelioma (PM); however, predictive or prognostic biomarkers remain unclear. We aimed to identify factors associated with survival in nivolumab-treated PM patients.

Methods: This retrospective, multi-institutional cohort study included patients with PM who received nivolumab monotherapy as a second-line or later treatment at 18 hospitals in Japan. We evaluated associations of progression-free survival (PFS) and overall survival (OS) with baseline clinical variables, protein expression in tumor tissue specimens obtained before first-line therapy by immunohistochemical (IHC), and tumor mutational and copy-number profiles detected by next-generation sequencing (NGS).

Results: Fifty-five patients were enrolled, with evaluable IHC in 42 and NGS in 33. V-domain immunoglobulin suppressor of T-cell activation (VISTA) expression was classified as high or low using a cutoff of 10% VISTA-positive tumor cells. High VISTA expression (n=35) was significantly associated with improved PFS and OS compared with low expression (n=7) (PFS: median, 5.1 vs 2.4 months, p = 0.001; OS: median, 12.8 vs 4.3 months, p = 0.007). Multivariate analysis confirmed high VISTA expression as an independent predictor of prolonged PFS and OS (PFS: hazard ratio [HR] 0.14, p < 0.001; OS: HR 0.38, p = 0.044).

Conclusion: Low tumor-cell VISTA expression was associated with poorer outcomes following nivolumab treatment; however, independent validation in prospective studies with a comparator arm is required before VISTA expression can be used to guide treatment selection. These findings support further investigation of biomarkers for combination strategies such as nivolumab-ipilimumab or chemoimmunotherapy in PM.

© 2026 Yokouchi et al.

In plain English

This retrospective study looked at 55 patients with pleural mesothelioma at 18 Japanese hospitals who received nivolumab alone after earlier treatment. Asbestos exposure was not studied. Tumor samples taken before first-line treatment were tested for the protein VISTA (42 patients) and gene changes (33). Tumors with at least 10% VISTA-positive cancer cells counted as high (35 patients); otherwise low (7). Median progression-free survival (time to worsening or death) was 5.1 months (95% CI, 3.5 to 6.7) for high VISTA versus 2.4 months (95% CI, 0 to 5.13) for low. Median overall survival was 12.8 (95% CI, 11.0 to 14.6) versus 4.3 months (95% CI, 1.2 to 7.3). After adjusting for other factors, both associations remained. PD-L1, HRD score, BAP1 and NF2 alterations, and CDKN2A homozygous deletion showed no significant survival link. The authors concluded low VISTA was associated with poorer outcomes after nivolumab. They noted the cutoff came from their own data, the low group was small, and no patients without nivolumab were compared. They called for prospective studies with such a comparison to show whether VISTA predicts nivolumab benefit specifically.

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: Retrospective, multi-institutional observational cohort study (exploratory biomarker study)
• Who was studied: 55 patients with pleural mesothelioma at 18 institutions in Japan, treated with nivolumab monotherapy as second-line or later treatment between August 2018 and October 2019. Tumor protein testing (IHC) was evaluable in 42 patients and gene sequencing (NGS) in 33. Median age was 69 years and 48 (87.3%) were male.
• Exposure: Asbestos exposure was not studied. The study looked at tumor-cell VISTA expression (high meaning 10% or more of tumor cells positive), other immune markers (PD-L1, TIM-3, LAG-3, OX40, CD4, CD8), tumor gene alterations and baseline clinical variables, all in patients receiving nivolumab monotherapy.
• Main results:
  • In all 55 patients, median progression-free survival was 4.8 months (95% CI, 3.6 to 6.0) and median overall survival was 12.3 months (95% CI, 10.3 to 14.4).
  • Median progression-free survival, measured to disease progression or death, was 5.1 months (95% CI, 3.5 to 6.7) in the VISTA-high group (n=35). In the VISTA-low group (n=7) it was 2.4 months (95% CI, 0 to 5.13), p=0.001.
  • Median overall survival was 12.8 months (95% CI, 11.0 to 14.6) in the VISTA-high group versus 4.3 months (95% CI, 1.2 to 7.3) in the VISTA-low group, p=0.007. All 7 VISTA-low patients had a progression event and died during follow-up.
  • In multivariate analysis of the 42-patient IHC set, high VISTA was associated with longer progression-free survival (HR 0.14, 95% CI 0.05 to 0.37, p less than 0.001). It was also associated with longer overall survival (HR 0.38, 95% CI 0.15 to 0.97, p=0.044).
  • With VISTA measured as a continuous value, each 10-percentage-point increase was associated with a lower risk of progression (HR 0.859, 95% CI 0.770 to 0.958, p=0.007). The association with overall survival was not statistically significant (HR 0.950, 95% CI 0.856 to 1.053, p=0.330). Using alternative cutoffs, the overall-survival association was significant only at 5%, 10% and 20%.
  • PD-L1 level (1% or more versus less than 1%) showed no significant difference in progression-free survival (5.1 vs 2.8 months, p=0.208) or overall survival (14.8 vs 9.3 months, p=0.093). TIM-3, LAG-3, OX40, CD4 and CD8 were not associated with survival.
  • Among the 33 sequenced patients, 16 (48.5%) had CDKN2A loss of heterozygosity or homozygous deletion, 16 (48.5%) had BAP1 alterations and 7 (21.2%) had NF2 alterations. Comparisons of high versus low HRD score, BAP1 wild-type versus altered, CDKN2A homozygous deletion versus none, and NF2 wild-type versus altered showed no significant survival differences.
• The authors' conclusion: The authors concluded that high tumor-cell VISTA expression was associated with longer progression-free and overall survival in this retrospective cohort of nivolumab-treated pleural mesothelioma patients. They said independent validation is needed before VISTA can guide treatment. They added that prospective studies with a non-ICI or non-nivolumab comparator arm are needed to determine whether VISTA has treatment-specific predictive value.
• Limitations the authors state:
  • Retrospective, observational, non-global study with a limited number of patients
  • Only patients with evaluable tumor specimens were included in the IHC and NGS analyses, which may introduce selection bias
  • The VISTA-low group had only 7 patients
  • The 10% cutoff was derived from this study's own data and needs validation in an independent cohort
  • No adjustment was made for multiple comparisons
  • There was no comparison group of patients not treated with nivolumab, so the data cannot show that VISTA specifically selects patients for nivolumab benefit
  • Residual or unmeasured confounding cannot be fully excluded, and the varied chemotherapy given before and after nivolumab could bias overall survival
  • Specimens were taken before first-line treatment, so they may not reflect the tumor just before nivolumab

Topics

Medical terms in this study, explained in our Lexicon: Nivolumab (Opdivo), Pleural Mesothelioma, Biomarker, Cohort Study, Progression-Free Survival, Overall Survival, First-line Therapy, Next-Generation Sequencing (NGS).

Related studies

• Prognostic Significance of B7-H3, TROP2, and p16 Expression in Pleural Mesothelioma: Clinicopathological Correlations and Survival Outcomes — N. Tas, R.O. Yüceer, et al. (2026)
• Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases — D.B. Chapel, J.J. Schulte, et al. (2021)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• The C-Reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma: A Retrospective Multi-institutional Study — S. Takamori, G. Toyokawa, et al. (2018)
• Combined grade and nuclear grade are prognosis predictors of epithelioid malignant peritoneal mesothelioma: a multi-institutional retrospective study — N. Benzerdjeb, P. Dartigues, et al. (2021)
• Prognostic Significance of B7-H3 Expression and CD163+ Tumor-Associated Macrophage Infiltration in Mesothelioma — T. Koç, R.O. Yüceer, et al. (2026)

Browse return to medical research.