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Updated: Nov 3, 2025
Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
V-Domain Ig Suppressor of T Cell Activation (VISTA) Expression Is an Independent Prognostic Factor in Multiple
Pim Mutsaers1, Hayri E Balcioglu2, Rowan Kuiper3
1Department of Hematology, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
Abstract:
Multiple myeloma (MM) is characterized by loss of anti-tumor T cell immunity. Despite moderate success of treatment with anti-PD1 antibodies, effective treatment is still challenged by poor T cell-mediated control of MM. To better enable identification of shortcomings in T-cell immunity that relate to overall survival (OS), we interrogated transcriptomic data of bone marrow samples from eight clinical trials (n = 1654) and one trial-independent patient cohort (n = 718) for multivariate analysis. Gene expression of V-domain Ig suppressor of T cell activation (VISTA) was observed to correlate to OS [hazard ratio (HR): 0.72; 95% CI: 0.61-0.83; p = 0.005]. Upon imaging the immune contexture of MM bone marrow tissues (n = 22) via multiplex in situ stainings, we demonstrated that VISTA was expressed predominantly by CD11b+ myeloid cells. The combination of abundance of VISTA+, CD11b+ cells in the tumor but not stromal tissue together with low presence of CD8+ T cells in the same tissue compartment, termed a high VISTA-associated T cell exclusion score, was significantly associated with short OS [HR: 16.6; 95% CI: 4.54-62.50; p < 0.0001]. Taken together, the prognostic value of a combined score of VISTA+, CD11b+ and CD8+ cells in the tumor compartment could potentially be utilized to guide stratification of MM patients for immune therapies.
Insights
A new study reveals that high levels of VISTA-expressing myeloid cells and low CD8+ T cells in multiple myeloma tumors predict poor survival. This finding could help stratify patients for immunotherapy.
Area of Science:
- Immunology
- Oncology
- Translational Research
Background:
- Multiple myeloma (MM) exhibits impaired anti-tumor T cell immunity, limiting treatment efficacy despite anti-PD1 therapies.
- Identifying T cell immunity deficits linked to overall survival (OS) is crucial for improving MM patient outcomes.
Purpose of the Study:
- To investigate T cell immunity shortcomings impacting OS in MM.
- To analyze transcriptomic data for prognostic biomarkers in MM.
Main Methods:
- Interrogated transcriptomic data from 1654 patients across 8 clinical trials and 718 patients in an independent cohort.
- Performed multivariate analysis on gene expression data, focusing on V-domain Ig suppressor of T cell activation (VISTA).
- Utilized multiplex in situ staining on 22 MM bone marrow tissues to analyze immune cell populations and spatial distribution.
Main Results:
- VISTA gene expression correlated with improved OS (HR: 0.72, p=0.005).
- VISTA was primarily expressed by CD11b+ myeloid cells in MM bone marrow.
- A high VISTA-associated T cell exclusion score (high VISTA+, CD11b+ cells; low CD8+ T cells in tumor tissue) was significantly associated with shorter OS (HR: 16.6, p<0.0001).
Conclusions:
- A combined prognostic score using VISTA+, CD11b+, and CD8+ cell presence in tumor tissue shows potential for patient stratification.
- This score could guide the selection of MM patients for immune therapies.
- Understanding the immune microenvironment is key to developing more effective MM treatments.
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