VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer

To identify additional immune inhibitory pathways in the prostate tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients on a pre-surgical clinical trial

Jianjun Gao

2017

Scholarcy highlights

  • Immune checkpoint therapies, including anti-CTLA-4 and anti-PD-1, that block T cell inhibitory pathways have led to durable anti-tumor responses and clinical benefit in a significant number of cancer patients 1,2
  • To better understand the immune profile within prostate tumors and potential compensatory immune inhibitory pathways that may arise in the setting of immune checkpoint monotherapy, we conducted a clinical trial with ipilimumab plus androgen deprivation therapy prior to surgery in patients with localized prostate cancer
  • We found a significantly greater immune cell infiltration in prostate tumors after ipilimumab therapy but not ADT, ADT monotherapy was associated with significantly higher inducible costimulator+ and granzymeB+ cells, which may reflect an activated T cell subset
  • We evaluated metastatic tumors and blood samples from patients with metastatic prostate cancer from a separate clinical trial who received treatment with ipilimumab and found an increase in PD-L1 and VISTA expression in tumor tissues as well as on monocytes in blood, which was similar to data from a mouse model of prostate cancer
  • All 17 patients experienced some type of immune-related adverse event; grade 3–4 irAEs occurred in 8/17 patients and consisted of colitis/diarrhea, hypophysitis, pancreatitis, and transaminitis, which were treated with corticosteroids and other immune-suppressive agents as previously described 13
  • Fresh peripheral blood mononuclear cells preparation, tumor single cell suspensions, and multiparameter flow cytometric analysis of T cell subsets including CD4, CD8, ICOS, Foxp, ICOS, PD-1, 4-1BB, OX40, CTLA-4, CD14, CD16, PD-L1, and VISTA, were carried out as we previously reported 6
  • Tumor tissues from metastatic castration resistant prostate cancer patients pre- and post-ipilimumab therapy were obtained from Institutional Review Board-approved clinical protocol MD Anderson Cancer Center 2013-0444

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