Adiponectin (APN), a cytokine constitutively produced in fat tissue, has been shown to exert anti‐inflammatory effects in various disease models. While the influence of APN on monocytic cells has been extensively studied in vitro, little is known about its role in T cells. In this study, we show that while <10% of human peripheral blood T cells express adiponectin receptors (AdipoRs) on their surface, most T cells store AdipoRs in intracellular compartments. AdipoRs colocalized with immune regulatory molecules CTLA‐4 and TIRC7 within clathrin‐coated vesicles. After stimulation, the expression of adiponectin receptor 1 (AdipoR1) and AdipoR2 was upregulated on the surface of antigen‐specific T cells, as determined by tetramer or CD137 staining, and AdipoR1 and AdipoR2 coexpressed with CTLA‐4. Addition of APN resulted in a significant diminution of antigen‐specific T‐cell expansion. Mechanistically, APN enhanced apoptosis and inhibited proliferation of antigen‐specific T‐cell lines. Further, APN directly inhibited cytokine production in response to antigen stimulation. In line with the in vitro data, APN‐deficient (knockout, KO) mice had higher frequencies of CD137⁺ T cells upon Coxsackie B virus infection. Altogether, our data suggest that APN is a novel negative T‐cell regulator. In contrast to the CTLA‐4 ligand B7 only expressed on APCs, APN is abundant in human plasma.

In this retrospective study, chimeric antigen receptor T cells remained effective in patients with relapsed/refractory large B-cell lymphoma after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines.

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (P = .004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, n = 15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, n = 6 (4%), and myelopathy, n = 5 (3%). PNS complications (32%) included neuropathies, n = 25 (17%), and myopathies and neuromuscular junction disorders, n = 23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P < .00001), and extensive chronic GVHD (HR, 3.2; P = .0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P < .0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT.

In this prospective randomized study, we compared the outcomes of single-unit umbilical cord blood transplantation (UCBT) and unmanipulated haploidentical stem cell transplantation (haplo-SCT) with post-transplantation cyclophosphamide (PTCy) in adults with hematologic malignancies. All patients received a myeloablative conditioning (MAC) regimen consisting of thiotepa, busulfan, and fludarabine, with antithymocyte globulin (ATG) added for UCBT recipients. Nineteen patients were randomized to UCBT and the other 26 to haplo-HSCT. Four patients (15%) allocated to the haplo-HSCT arm lacked a suitable donor and were crossed over to the UCBT arm. Finally, 23 underwent UCBT and 22 underwent haplo-HSCT. The cumulative incidence of neutrophil recovery was 87% at a median of 19 days (range, 13 to 24 days) in the UCBT arm versus 100% at a median of 17 days (range, 13 to 25 days) in the haplo-SCT arm (P = .04). Platelet recovery was 70% at a median of 40 days (range, 18 to 129 days) in the UCBT arm versus 86% at a median of 24 days (range, 12 to 127 days) in the haplo-HCT arm (P = .02). Rates of acute graft-versus-host disease (GVHD) grade II-IV or grade III-IV, overall chronic GVHD, and extensive chronic GVHD in the UCBT and Haplo-SCT arms were 43% versus 36% (P = .8), 9% versus 9% (P = 1), 66% versus 43% (P = .04), and 41% versus 23% (P = .2), respectively. Two-year nonrelapse mortality and relapse in the 2 arms were 52% versus 23% (P = .06) and 17% versus 23% (P = .5), respectively. Two-year disease-free survival, overall survival, and GVHD/relapse-free survival in the 2 arms were 30% versus 54% (P = .2), 35% versus 59% (P = .1), and 17% versus 40% (P = .04), respectively. Our data show that in the context of an MAC regimen, haplo-SCT with PTCy provides improved outcomes compared with ATG-containing single-unit UCBT.

EBV infection leads to life‐long viral persistence. Although EBV infection can result in chronic disease and malignant transformation, most carriers remain disease‐free as a result of effective control by T cells. EBV‐specific IFN‐γ‐producing T cells could be demonstrated in acute and chronic infection as well as during latency. Recent studies, however, provide evidence that assessing IFN‐γ alone is insufficient to assess the quantity and quality of a T‐cell response. Using overlapping peptide pools of latent EBV nuclear antigen 1 and lytic BZLF‐1 protein and multicolor flow cytometry, we demonstrate that the majority of ex vivo EBV‐reactive T cells in healthy virus carriers are indeed IL‐2‐ and/or TNF‐producing memory cells, the latter being significantly more frequent in BM. After in vitro expansion, a substantial number of EBV‐specific CD4⁺ and CD8⁺ T cells retained a CC‐chemokine receptor 7 (CCR7)‐positive memory phenotype. Based on their cytokine profiles, six different EBV‐specific T‐cell subsets could be distinguished with TNF‐single or TNF/IL‐2‐double producing cells expressing the highest CCR7 levels resembling early‐differentiated memory T cells. Our study delineates the memory T‐cell profile of a protective immune response and provides a basis for analyzing T‐cell responses in EBV‐associated diseases.