High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System.

RATIONALE: Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood. OBJECTIVE: To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema. METHODS: We used single-cell mass cytometry to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 controls. Imaging mass cytometry (IMC) was applied to identify altered cell-cell interactions in alveolar tissue from emphysema patients (n=12) compared to controls (n=8). MEASUREMENTS AND MAIN RESULTS: We observed higher percentages of central memory CD4 T cells in combination with lower proportions of effector memory CD4 T cells in emphysema. In addition, proportions of cytotoxic central memory CD8 T cells and CD127+CD27+CD69- T cells were higher in emphysema, the latter potentially reflecting an influx of circulating lymphocytes into the lungs. Central memory CD8 T cells, isolated from alveolar tissue from emphysema patients exhibited an IFN-γ-response upon anti-CD3/anti-CD28 activation. Proportions of CD1c+ dendritic cells (DC), expressing migratory and costimulatory markers, were higher in emphysema. Importantly, IMC enabled us to visualize increased spatial colocalization of CD1c+ DC and CD8 T cells in emphysema in situ. CONCLUSION: Using single-cell CyTOF, we characterized the alterations of the immune cell signature in alveolar tissue from patients with COPD stage III/IV emphysema versus control lung tissue. These data contribute to a better understanding of the pathogenesis of emphysema and highlight the feasibility of interrogating the immune cell signature using single-cell and IMC in human lung tissue.

CD4+ T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors.

CD4+ T cells can "help" or "license" conventional type 1 dendritic cells (cDC1s) to induce CD8+ cytotoxic T lymphocyte (CTL) anticancer responses, as proven in mouse models. We recently identified cDC1s with a transcriptomic imprint of CD4+ T-cell help, specifically in T-cell-infiltrated human cancers, and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy. Here, we delineate the mechanism of cDC1 licensing by CD4+ T cells in humans. Activated CD4+ T cells produce IFNß via the STING pathway, which promotes MHC-I antigen (cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses. In cooperation with CD40 ligand (L), IFNß also optimizes the costimulatory and other functions of cDC1s required for CTL response induction. IFN-I-producing CD4+ T cells are present in diverse T-cell-infiltrated cancers and likely deliver "help" signals to CTLs locally, according to their transcriptomic profile and colocalization with "helped/licensed" cDCs and tumor-reactive CD8+ T cells. In agreement with this scenario, the presence of IFN-I-producing CD4+ T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

Immune checkpoints targeting dendritic cells for antibody-based modulation in cancer.

Dendritic cells (DC) are professional antigen-presenting cells which link innate to adaptive immunity. DC play a central role in regulating antitumor T-cell responses in both tumor-draining lymph nodes (TDLN) and the tumor microenvironment (TME). They modulate effector T-cell responses via immune checkpoint proteins (ICPs) that can be either stimulatory or inhibitory. Functions of DC are often impaired by the suppressive TME leading to tumor immune escape. Therefore, better understanding of the mechanisms of action of ICPs expressed by (tumor-infiltrating) DC will lead to potential new treatment strategies. Genetic manipulation and high-dimensional analyses have provided insight in the interactions between DC and T-cells in TDLN and the TME upon ICP targeting. In this review, we discuss (tumor-infiltrating) DC lineage cells and tumor tissue specific "mature" DC states and their gene signatures in relation to anti-tumor immunity. We also review a number of ICPs expressed by DC regarding their functions in phagocytosis, DC activation, or inhibition and outline position in, or promise for clinical trials in cancer immunotherapy. Collectively, we highlight the critical role of DC and their exact status in the TME for the induction and propagation of T-cell immunity to cancer.

A floating-gate field-effect transistor memory device based on organic crystals with a built-in tunneling dielectric by a one-step growth strategy.

A floating-gate organic field-effect transistor (FG-OFET) memory device is becoming a promising candidate for emerging non-volatile memory applications due to the advantages of its sophisticated data-storage mechanism and reliable long-term data retention capacity. However, a conventional FG-OFET memory device suffers from complex fabrication technologies and poor mechanical flexibility, which limits its practical applications. Here, we propose a facile one-step liquid-surface drag coating strategy to fabricate a layered stack of 2,8-difluoro-5,11-bis(triethylsilylethynyl) anthradithiophene (Dif-TES-ADT) crystals and high-quality insulating polymer polystyrene (PS). The liquid surface enhances the spreading area of an organic solution and facilitates the unidirectional growth of organic crystals. In the bilayer-structured blend, the bottom PS polymer and the top Dif-TES-ADT semiconductor serve as a tunneling dielectric and an active memory layer of an FG-OFET memory device, respectively. Consequently, a flexible FG-OFET memory device with a large memory window of 41.4 V, a long retention time of 5000 s, and a high current ON/OFF ratio of 105 could be achieved, showing the best performance ever reported for organic thin film-based FG-OFET memory devices. In addition, multi-level data storage (3 bits per cell) can be achieved by tuning the gate voltage magnitude. Our work not only provides a general strategy for the growth of high-quality organic crystals, but also paves the way towards high-performance flexible memory devices.

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses.

CD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment.

Despite their low abundance in the tumor microenvironment (TME), classical type 1 dendritic cells (cDC1) play a pivotal role in anti-cancer immunity, and their abundance positively correlates with patient survival. However, their interaction with CD4+ T-cells to potentially enable the cytotoxic T lymphocyte (CTL) response has not been elucidated. Here we show that contact with activated CD4+ T-cells enables human ex vivo cDC1, but no other DC types, to induce a CTL response to cell-associated tumor antigens. Single cell transcriptomics reveals that CD4+ T-cell help uniquely optimizes cDC1 in many functions that support antigen cross-presentation and T-cell priming, while these changes don't apply to other DC types. We robustly identify "helped" cDC1 in the TME of a multitude of human cancer types by the overlap in their transcriptomic signature with that of recently defined, tumor-infiltrating DC states that prove to be positively prognostic. As predicted from the functional effects of CD4+ T-cell help, the transcriptomic signature of "helped" cDC1 correlates with tumor infiltration by CTLs and Thelper(h)-1 cells, overall survival and response to PD-1-targeting immunotherapy. These findings reveal a critical role for CD4+ T-cell help in enabling cDC1 function in the TME and may establish the helped cDC1 transcriptomic signature as diagnostic marker in cancer.

Radiomics-based signature of breast cancer on preoperative contrast-enhanced MRI to predict axillary metastasis.

Aim: This study aimed to predict axillary metastasis using radiology features in dynamic contrast-enhanced MRI. Methods: This study included 243 breast lesions confirmed as malignant based on axillary status. Most outcome-predictive features were selected using four machine-learning algorithms. Receiver operating characteristic analysis was used to reflect diagnostic performance. Results: Least absolute shrinkage and selection operator was used to dimensionally reduce 1137 radiomics features to three features. Three optimal radiomics features were used to model construction. The logistic regression model achieved an accuracy of 97% and 85% in the training and test groups. Clinical utility was evaluated using decision curve analysis. Conclusion: The novel combination of radiomics analysis and machine-learning algorithm could predict axillary metastasis and prevent invasive manipulation.

Autophagy Mediates MMP-2 Expression in Glaucomatous Trabecular Meshwork Cells.

Purpose: To investigate the effect of 3-methyladenine (3-MA) and starvation on the expression of matrix metalloproteinase (MMP-2) in patients with primary open-angle glaucoma. Methods: Primary TM cells were cultured and divided into three groups. The control group was treated with a normal medium, the 3-MA group was stimulated with 3-MA, and the starvation group received nutrient depletion by replacing the normal media with Earle's balanced salt solution. Cellular mRNA and protein were measured at different 3-MA concentrations and starvation time periods. The level of autophagy was accessed by monodansylcadaverine fluorescent staining and expression of specific autophagy-related genes, light chain 3 (LC3), and Beclin1. The effects of 3-MA and starvation on cell proliferation were determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay kit. The mRNA and protein expression of LC3-II, Beclin1, and MMP-2 were measured by reverse transcription-polymerase chain reaction and western blot, respectively. Results: Compared to the control group, starvation significantly upregulated LC3-II and Beclin1 in TM cells after 3 h of stimulation, which peaked at 6 h and 9 h, respectively. Increased MDC-labeled cells were also observed. Starvation downregulated the expression of MMP-2. On the contrary, 3-MA suppressed the activation of autophagy, as shown by the marked downregulation of LC3-II and Beclin1. The expressions of MMP-2 were higher in the 3-MA group compared to the control group, reaching a peak at a concentration of 5 mM. Conclusion: Autophagy may be involved in the pathogenesis of POAG via regulating the expression of MMP-2 and, subsequently, the deposition of the extracellular matrix.

Trial watch: Dendritic cell (DC)-based immunotherapy for cancer.

Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to recent paradigm-shifts in immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed to tumor-associated or -specific antigens (TAAs or TSAs), in the presence of immunostimulatory molecules to induce DC maturation, followed by reinfusion into patients. Accordingly, DC vaccines can induce TAA/TSA-specific CD8+/CD4+ T cell responses. Yet, DC vaccination still shows suboptimal anti-tumor efficacy in the clinic. Extensive efforts are ongoing to improve the immunogenicity and efficacy of DC vaccines, often by employing combinatorial chemo-immunotherapy regimens. In this Trial Watch, we summarize the recent preclinical and clinical developments in this field and discuss the ongoing trends and future perspectives of DC-based immunotherapy for oncological indications.

A Novel Technique With Ileal Mesentery to Reconstruct the Pelvic Peritoneum After Pelvic Dissection With End Colostomy for Rectal Cancer.

BACKGROUND: After abdominoperineal resection, low anterior resection, and end colostomy for lower rectal cancer, it is necessary to reconstruct the pelvic peritoneum to avoid small bowel obstruction, perineal hernia, and radiation enteritis in patients for whom postoperative radiotherapy is planned. However, pelvic peritoneal closure is technically difficult in patients who lack enough peritoneum to cover the defect or have received neoadjuvant radiation and have a rigid pelvis. IMPACT OF INNOVATION: The impact of this innovation is to reconstruct the pelvic peritoneum with the distal ileal mesentery laparoscopically. TECHNOLOGY, MATERIALS AND METHODS: After removal of the tumor, the distal ileal mesentery was selected to completely cover the defect. Subsequently, suturing of the ileal mesentery to the posterior wall of the urinary bladder and all sides of the pelvic cavity was performed. Finally, the patients were returned to the headfirst supine position to ensure that there was no small bowel falling into the pelvic dead space. PRELIMINARY RESULTS: All surgical procedures were successfully performed laparoscopically from January 2019 to April 2021. No perineal complications or intestinal obstructions occurred during the follow-up period. CONCLUSIONS AND FUTURE DIRECTIONS: This novel technique was found to be safe and effective. Moreover, it provided an economical method for the reconstruction of the pelvic peritoneum using autologous material, which could preserve the small intestine in the abdomen to avoid related complications. Additional larger series of patients with longer follow-up are needed to validate the safety and feasibility of this method.

A Fully Solution-Printed Photosynaptic Transistor Array with Ultralow Energy Consumption for Artificial-Vision Neural Networks.

Photosynaptic organic field-effect transistors (OFETs) represent a viable pathway to develop bionic optoelectronics. However, the high operating voltage and current of traditional photosynaptic OFETs lead to huge energy consumption greater than that of the real biological synapses, hindering their further development in new-generation visual prosthetics and artificial perception systems. Here, a fully solution-printed photosynaptic OFET (FSP-OFET) with substantial energy consumption reduction is reported, where a source Schottky barrier is introduced to regulate charge-carrier injection, and which operates with a fundamentally different mechanism from traditional devices. The FSP-OFET not only significantly lowers the working voltage and current but also provides extraordinary neuromorphic light-perception capabilities. Consequently, the FSP-OFET successfully emulates visual nervous responses to external light stimuli with ultralow energy consumption of 0.07-34 fJ per spike in short-term plasticity and 0.41-19.87 fJ per spike in long-term plasticity, both approaching the energy efficiency of biological synapses (1-100 fJ). Moreover, an artificial optic-neural network made from an 8 × 8 FSP-OFET array on a flexible substrate shows excellent image recognition and reinforcement abilities at a low energy cost. The designed FSP-OFET offers an opportunity to realize photonic neuromorphic functionality with extremely low energy consumption dissipation.

Organic Semiconductor Crystal Engineering for High-Resolution Layer-Controlled 2D Crystal Arrays.

2D organic semiconductor crystals (2DOSCs) have extraordinary charge transport capability, adjustable photoelectric properties, and superior flexibility, and have stimulated continuous research interest for next-generation electronic and optoelectronic applications. The prerequisite for achieving large-area and high-throughput optoelectronic device integration is to fabricate high-resolution 2DOSC arrays. Patterned substrate- and template-assisted self-assembly is an effective strategy to fabricate OSC arrays. However, the film thickness is difficult to control due to the complicated crystallization process during solvent evaporation. Therefore, the manufacturing of 2DOSC arrays with high-resolution and controllable molecular-layer numbers through solution-based patterning methods remains a challenge. Herein, a two-step strategy to produce high-resolution layer-controlled 2DOSC arrays is reported. First, large-scale 2DOSCs with well-defined layer numbers are obtained by a solution-processed organic semiconductor crystal engineering method. Next, the high-resolution layer-controlled 2DOSC arrays are fabricated by a polydimethylsiloxane mold-assisted selective contact evaporation printing technique. The organic field-effect transistors (OFETs) based on 2DOSC arrays have high electrical performance and excellent uniformity. The 2,6-bis(4-hexylphenyl)anthracene 2DOSC arrays-based OFETs have a small variation of 12.5% in mobility. This strategy can be applied to various organic semiconductors and pattern arrays. These demonstrations will offer more opportunities for 2DOSCs for integrated optoelectronic devices.

Laparoscopic right hemicolectomy with complete mesocolic excision plus D3 lymphadenectomy (CME + D3): a new medial approach for central vascular ligation.

Due to the high risk of vascular injuries, it remains a technical challenge and time-consuming procedure for surgeons to perform CME and D3 lymph node dissection in laparoscopic right hemicolectomy. To overcome this difficulty, we developed a novel method of the vessel's management for central vascular ligation (CVL). The key feature of this new approach focused on vascular dissection in two aspects. The first one was to expose the superior mesentery vein (SMV) and the branches of the superior mesentery artery (SMA) at their roots from left to right after dividing the peritoneum near the left border of SMV, which has the advantage of exposing SMV and controlling bleeding. The second was to selectively ligate the colic tributaries of gastrocolic trunk of Henle (GTH) after expanding its surrounding spaces. We named this technique the "new approach (NA)". Thirty-eight patients who underwent laparoscopic right hemicolectomy with the new approach (NA) were retrospectively analyzed and compared with data from 35 patients, who underwent the conventional medial approach (TA) performed by the same surgical team from April 2017 to March 2021. There was no significant difference between the two groups in baseline data (all p > 0.05). All 38 operations were completed with this procedure successfully. The NA approach was associated with a shorter operation time (190.5 min vs.215.5 min; P < 0.05) and a smaller blood loss (50 ml vs. 95 ml; P < 0.05) compared with the conventional approach. Two cases of vascular injuries occurred in the TA group and had been managed laparoscopically. The lymph nodes count (15 vs. 16; P > 0.05) was not significantly different; additionally, no difference was observed regarding anastomotic leakage (both n = 0) and postoperative complications (3/31 vs. 3/30; P > 0.05). No mortality was observed. NA is feasible and can be an optional method of vessel's management in laparoscopic CME and D3 lymphadenectomy for right-sided colon cancer.

A questionnaire-based validation of metacognitive strategies in writing and their predictive effects on the writing performance of English as foreign language student writers.

Introduction: This study-drawing upon data from a questionnaire-examined 503 Chinese university students' metacognitive strategies in writing (MSW). The focus was on Chinese student writers who are learning English as a foreign language (EFL). Methods: The examination was conducted through a survey on MSW and a writing test administered at the end of the semester. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for data analysis. Multiple regression analysis was also adopted for understanding the predictive effects of strategies on writing performance. Results: The findings provided validity to MSW, including person, task, strategies, planning, monitoring, and evaluating. The different components of MSW were reported to significantly affect the participants' writing performance. The findings highlight that EFL student writers were aware of metacognitive writing strategies. The MSW survey could be used to assess EFL students' metacognitive writing strategies and develop curricula in writing strategy training. Conclusion: Writing instruction can direct learners' ability to acquire metacognitive writing strategies, particularly those of planning, monitoring, and evaluating, to build their awareness as agents in EFL writing. Relevant pedagogical implications are discussed.

People living with HIV easily lose their immune response to SARS-CoV-2: result from a cohort of COVID-19 cases in Wuhan, China.

BACKGROUND: To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. METHODS: In this cohort study, COVID-19 patients admitted to hospitals in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every 15 days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. RESULTS: Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among patients with moderate disease (AOR = 0.24, 95% CI 0.07-0.85). PLWH had a lower IgG seroconversion rate (AOR = 0.11, 95% CI 0.03-0.39) and shorter IgG duration (AHR = 3.99, 95% CI 1.43-11.13) compared to HIV-naïve individuals. Patients with higher lymphocyte counts at onset had a lower positive conversion rate (AOR = 0.30, 95% CI 0.10-0.87) and shorter duration for IgG (AHR = 4.01, 95% CI 1.78-9.02). CONCLUSIONS: The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH.

People Living with HIV Easily lose their Immune Response to SARS-CoV-2: Result From A Cohort of COVID-19 Cases in Wuhan, China.

Background To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. Methods In this cohort study, COVID-19 patients admitted to hospital in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every fifteen days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. Results Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among moderate patients (AOR = 0.18, 95% CI: 0.05-0.65) and PLWH had a lower IgG seroconversion rate compared to the HIV-naive group (AOR = 0.22, 95% CI: 0.05-0.90). Patients with lower lymphocyte counts at onset had a higher positive conversion rate (AOR = 0.29, 95% CI: 0.09-0.90) and longer duration for IgG (AHR = 4.01, 95% CI: 1.78-9.02). Conclusions The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH, which meant PLWH was in a disadvantaged situation when affected with COVID-19.

Flagellin/TLR5 Stimulate Myeloid Progenitors to Enter Lung Tissue and to Locally Differentiate Into Macrophages.

Toll-like receptor 5 (TLR5) is the receptor of bacterial Flagellin. Reportedly, TLR5 engagement helps to combat infections, especially at mucosal sites, by evoking responses from epithelial cells and immune cells. Here we report that TLR5 is expressed on a previously defined bipotent progenitor of macrophages (MΦs) and osteoclasts (OCs) that resides in the mouse bone marrow (BM) and circulates at low frequency in the blood. In vitro, Flagellin promoted the generation of MΦs, but not OCs from this progenitor. In vivo, MΦ/OC progenitors were recruited from the blood into the lung upon intranasal inoculation of Flagellin, where they rapidly differentiated into MΦs. Recruitment of the MΦ/OC progenitors into the lung was likely promoted by the CCL2/CCR2 axis, since the progenitors expressed CCR2 and type 2 alveolar epithelial cells (AECs) produced CCL2 upon stimulation by Flagellin. Moreover, CCR2 blockade reduced migration of the MΦ/OC progenitors toward lung lavage fluid (LLF) from Flagellin-inoculated mice. Our study points to a novel role of the Flagellin/TLR5 axis in recruiting circulating MΦ/OC progenitors into infected tissue and stimulating these progenitors to locally differentiate into MΦs. The progenitor pathway to produce MΦs may act, next to monocyte recruitment, to fortify host protection against bacterial infection at mucosal sites.

Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses.

Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34+ hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141+CLEG9A+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-α. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients.