Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester: case report and review of the literature.

Although T-cell checkpoint blockade has revolutionized melanoma therapy, metastatic melanoma in pregnancy remains a challenging area of unmet need. Treatment with anti-PD1 therapy decreases foetal-maternal tolerance and increases the risk of pregnancy loss in animal studies and is considered category D by the Food and Drug Administration. We describe a unique case of conception and pregnancy, with successful maternal and foetal outcomes, in a patient with metastatic melanoma who had received combination anti-CTLA-4 and anti-PD1 therapy. A 32-year-old G0P0 lady, with a 10-year history of infertility of unclear cause, was found to be 7 weeks pregnant after 14 months of nivolumab maintenance therapy, having previously received combination ipilimumab and nivolumab. Nivolumab was ceased upon discovery of pregnancy in the first trimester. The patient had an uneventful pregnancy, followed by spontaneously premature labour, and delivered by caesarean section at 33 weeks' gestation. The foetus had moderate intrauterine growth restriction, as well as congenital hypothyroidism, which possibly constitutes the first documented case of foetal immune-related adverse event from maternal anti-PD1 exposure. No adverse events were noted in the mother. At 6 months of follow-up postpartum, the mother had a sustained complete response to treatment, and the baby had appropriate weight gain with normal developmental milestones. We summarize and discuss the available literature of immune checkpoint inhibitor exposure in pregnancy, which consists of a total of three case reports.

Use of CD107-based cell sorting ex vivo to enrich subdominant CD8+ T cells in culture.

CD8+ T lymphocytes are key effectors in the control of viral diseases and some tumours. In general, the majority of CD8+ T cells recognize a few immunodominant epitopes, but in some circumstances, subdominant specificities may be more relevant as targets for vaccines or immunotherapy. Epstein-Barr virus (EBV)-associated cancers are an example where knowledge of subdominant-specific CD8+ T cells is important because the immunodominant EBV proteins are not expressed in these cancers. We have developed a live-cell sorting method based on CD107 detection to remove CD8+ T cells recognising dominant EBV epitopes and show that this allows enrichment of subdominant-specific CD8+ T cells in subsequent cultures. This work shows that immunodomination in vitro suppresses the outgrowth of subdominant-specific CD8+ T cells in culture. The method may have broad applications for finding subdominant targets for immunotherapy and vaccines, and the principle suggests a means of improving subdominant CD8+ T-cell cultures grown for immunotherapy.