VSIR

Overview

VSIR (V-Set Immunoregulatory Receptor), also known as C10orf54 and VISTA, encodes an immune checkpoint receptor expressed on T cells and myeloid cells. In the nivolumab pharmacodynamic study (CA209-038), VSIR was among the immune checkpoint genes selectively upregulated on-therapy in responders, nominating it as a candidate target for combination immunotherapy strategies.

Alterations observed in the corpus

  • VSIR (C10orf54 / VISTA) is selectively upregulated on-therapy in responders (CR/PR) but not non-responders during nivolumab treatment of advanced melanoma; among 2670 differentially expressed genes distinguishing responder vs non-responder on-therapy dynamics (q < 0.20) PMID:29033130.

Cancer types (linked)

  • SKCM — responder-selective on-therapy upregulation in the CA209-038 prospective trial (NCT01621490) of nivolumab (3 mg/kg q2w) in 68 advanced melanoma patients; the upregulation is specific to CR/PR patients and absent in SD/PD patients PMID:29033130.

Co-occurrence and mutual exclusivity

  • VSIR upregulation on-therapy co-occurs with upregulation of other checkpoint receptors — TNFRSF4 (OX40), TIGIT, and HAVCR2 (TIM-3) — selectively in responders, suggesting coordinated secondary checkpoint induction following anti-PD-1 therapy PMID:29033130.

Therapeutic relevance

  • Responder-selective on-therapy upregulation of VSIR in melanoma patients responding to nivolumab nominates it as a candidate target for combination immunotherapy; co-blockade of VSIR with PD-1 blockade is proposed as a rational next therapeutic strategy PMID:29033130.

Open questions

  • Whether VSIR upregulation is a cause or consequence of the immunoediting response is unresolved; clinical testing of anti-VISTA combination therapy with anti-PD-1 agents is nominated but not yet validated in this corpus PMID:29033130.

Sources

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