TNFR2 blockade of regulatory T cells unleashes an antitumor immune response after hematopoietic stem-cell transplantation.

BACKGROUND: Targeting immune checkpoints that inhibit antitumor immune responses has emerged as a powerful new approach to treat cancer. We recently showed that blocking the tumor necrosis factor receptor-type 2 (TNFR2) pathway induces the complete loss of the protective function of regulatory T cells (Tregs) in a model of graft-versus-host disease (GVHD) prevention that relies on Treg-based cell therapy. Here, we tested the possibility of amplifying the antitumor response by targeting TNFR2 in a model of tumor relapse following hematopoietic stem-cell transplantation, a clinical situation for which the need for efficient therapeutic options is still unmet. METHOD: We developed appropriate experimental conditions that mimic patients that relapsed from their initial hematological malignancy after hematopoietic stem-cell transplantation. This consisted of defining in allogeneic bone marrow transplantation models developed in mice, the maximum number of required tumor cells and T cells to infuse into recipient mice to develop a model of tumor relapse without inducing GVHD. We next evaluated whether anti-TNFR2 treatment could trigger alloreactivity and consequently antitumor immune response. In parallel, we also studied the differential expression of TNFR2 on T cells including Treg from patients in post-transplant leukemia relapse and in patients developing GVHD. RESULTS: Using experimental conditions in which neither donor T cells nor TNFR2-blocking antibody per se have any effect on tumor relapse, we observed that the coadministration of a suboptimal number of T cells and an anti-TNFR2 treatment can trigger alloreactivity and subsequently induce a significant antitumor effect. This was associated with a reduced percentage of activated CD4+ and CD8+ Tregs. Importantly, human Tregs over-expressed TNFR2 relative to conventional T cells in healthy donors and in patients experiencing leukemia relapse or cortico-resistant GVHD after hematopoietic stem cell transplantation. CONCLUSIONS: These results highlight TNFR2 as a new target molecule for the development of immunotherapies to treat blood malignancy relapse, used either directly in grafted patients or to enhance donor lymphocyte infusion strategies. More widely, they open the door for new perspectives to amplify antitumor responses against solid cancers by directly targeting Tregs through their TNFR2 expression.

Radiation Therapy Department Reorganization during the Coronavirus Disease 2019 (COVID-19) Outbreak: Keys to Securing Staff and Patients During the First Weeks of the Crisis and Impact on Radiation Therapy Practice from a Single Institution Experience.

PURPOSE: During the first weeks of the coronavirus disease 2019 (COVID-19) outbreak in France, it was necessary to clearly define organizational priorities in the radiation therapy (RT) departments. In this report, we focus on the urgent measures taken to reduce risk for both our staff and patients by reducing the number of patients receiving treatment. METHODS AND MATERIALS: We reviewed the fractionation schemes for all patients in our department, including those receiving treatment and those soon to start treatment. Our goals were to (1) decrease the number of patients coming daily to the hospital for RT, (2) adapt our human resources to continue patients' care in the department, and (3) help to cover understaffed COVID-19 sectors of the hospital. RESULTS: We identified 50 patients who were receiving treatment (n = 6), were going to start radiation after CT scan simulation (n = 41), or for whom the CT scan was pending (n = 3). The majority were women (64%) treated for breast cancer (54%). RT was delayed for 22 (44%) patients. The majority were offered hormone therapy as "waiting therapy." Hypofractionation was considered in 21 (42%) patients mainly with breast cancer (18 of 21, 86%). The number of courses initially planned and replanned as a result of the COVID-19 outbreak during the period of March 15 to May 31, 2020, were 1383 and 683, respectively, which represented a reduction of 50% (including delayed sessions) that allowed our reorganization process. CONCLUSIONS: To conserve resources during the pandemic, we successfully reduced the number of patients receiving treatment in a proactive fashion and adapted our organization to minimize the risk of COVID-19 contamination. Departments across the world may benefit from this same approach.

Patient radiation doses and reference levels in pediatric interventional radiology.

OBJECTIVES: To describe, in a multicentric paediatric population, reference levels (RLs) for three interventional radiological procedures. METHODS: From January 2012 to March 2015, children scheduled for an interventional radiological procedure in two French tertiary centres were retrospectively included and divided into four groups according to age: children younger than 2 years (A1), aged 2-7 years (A5), 8-12 years (A10) and 13-18 years (A15). Three procedures were identified: cerebral digital subtraction angiography (DSA), brain arteriovenous malformation (bAVM) embolization, and head and neck superficial vascular malformation (SVM) percutaneous sclerotherapy. Demographic and dosimetric data, including dose area product (DAP), were collected. RESULTS: 550 procedures were included. For DSA (162 procedures), the proposed RL values in DAP were 4, 18, 12 and 32 Gy∙cm2 in groups A1, A5, A10 and A15, respectively. For bAVM embolization (258 procedures), values were 33, 70, 105 and 88 Gy∙cm2 in groups A1, A5, A10 and A15, respectively. For SVM sclerotherapy (130 procedures), values were 350, 790, 490 and 248 mGy∙cm2 in groups A1, A5, A10 and A15, respectively. CONCLUSION: Consecutive data were available to permit a proposal of reference levels for three major paediatric interventional radiology procedures. KEY POINTS: • We determined reference levels (RLs) for bAVM embolization, DSA and SVM sclerotherapy. • The proposed RLs will permit benchmarking practice with an external standard. • The proposed RLs by age may help to develop paediatric dose guidelines.