Edited by Alex Toker

Manipulation of co-stimulatory or co-inhibitory checkpoint proteins allows for the reversal of tumor-induced T-cell anergy observed in cancer. The field has gained credence given success with CTLA-4 and PD-1 inhibitors. These molecules include immunoglobulin family members and the B7 subfamily as well as the TNF receptor family members. PD-L1 inhibitors and LAG-3 inhibitors have progressed through clinical trials. Other B7 family members have shown promise in preclinical models. TNFR superfamily members have shown variable success in preclinical and clinical studies. As clinical investigation in tumor immunology gains momentum, the next stage becomes learning how to combine checkpoint inhibitors and agonists with each other as well as with traditional chemotherapeutic agents.

: Ovarian vein thrombosis (OVT) remains poorly understood with no consensus regarding its importance or treatment. In this retrospective study, we investigated the clinical features, risk factors, treatment patterns, and prognosis of patients with OVT, including venous thromboembolism (VTE) recurrences. Adult patients who presented to our medical center with an identifiable diagnosis of OVT over a 10-year period were included in this retrospective observational study. Individual patient charts were reviewed to collect baseline and outcomes data. We identified 223 women with OVT. Median follow-up was 857 days. Only 36.6% presented with abdominal pain and 61.4% reported a history of gynecologic surgery. Overall, right or left OVT incidence was similar (44.6 and 41.4%, respectively) but peripartum patients were more likely to have right OVT (60.0%, P = 0.03). VTE recurred in 22 (9.9%) women, all of which were remote from the OVT and there were no recurrences in peripartum patients. Mean (± SD) time to recurrence was 409 (± 421) days. Only 7.6% of OVT patients were anticoagulated for OVT; these women had a 38% reduction in VTE recurrence but because of low numbers, this was not statistically significant. VTE recurrence after OVT was associated with greater mortality in all patients, including patients with cancer. OVT is associated with an increased rate of non-OVT recurrence. Peripartum OVT patients appear to constitute a different patient population as they were younger, exhibited different risk factors, and had no increased incidence of recurrence. Although only a minority of patients with OVT was anticoagulated, this group had a reduction in VTE recurrence. A prospective study is needed to determine the utility of anticoagulation for women with OVT.

The epichaperome is a new cancer target composed of hyperconnected networks of chaperome members that facilitate cell survival. Cancers with an altered chaperone configuration may be susceptible to epichaperome inhibitors. We developed a flow cytometry-based assay for evaluation and monitoring of epichaperome abundance at the single cell level, with the goal of prospectively identifying patients likely to respond to epichaperome inhibitors, to measure target engagement, and dependency during treatment. As proof of principle, we describe a patient with an unclassified myeloproliferative neoplasm harboring a novel PML-SYK fusion, who progressed to acute myeloid leukemia despite chemotherapy and allogeneic stem cell transplant. The leukemia was identified as having high epichaperome abundance. We obtained compassionate access to an investigational epichaperome inhibitor, PU-H71. After 16 doses, the patient achieved durable complete remission. These encouraging results suggest that further investigation of epichaperome inhibitors in patients with abundant baseline epichaperome levels is warranted.

No abstract