V-Domain Ig Suppressor of T Cell Activation (VISTA) Expression Is an Independent Prognostic Factor in Multiple Myeloma

• Main Authors: Pim Mutsaers, Hayri E. Balcioglu, Rowan Kuiper, Dora Hammerl, Rebecca Wijers, Mark van Duin, Bronno van der Holt, Annemiek Broijl, Walter Gregory, Sonja Zweegman, Pieter Sonneveld, Reno Debets
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Cancers
• Subjects: multiple myeloma; tumor immunology; immune therapy; V-domain Ig suppressor of T cell activation (VISTA); immune checkpoints
• Online Access: https://www.mdpi.com/2072-6694/13/9/2219

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 (<i>n</i> = 1654) and one trial-independent patient cohort (<i>n</i> = 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; <i>p</i> = 0.005]. Upon imaging the immune contexture of MM bone marrow tissues (<i>n</i> = 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 <i>VISTA-associated T cell exclusion</i> score, was significantly associated with short OS [HR: 16.6; 95% CI: 4.54–62.50; <i>p</i> < 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.