BACKGROUND:B cell maturation antigen (BCMA) is a key therapeutic target in multiple myeloma (MM), yet its whole-body in vivo distribution and role in disease assessment remain incompletely defined. We aimed to evaluate the safety, diagnostic performance, and clinical utility of a novel BCMA-targeted PET tracer, 68Ga-PFBC01, in patients with plasma cell disorders. METHODS:We conducted a single-center, prospective, single-arm phase I trial (ClinicalTrials.gov NCT06717113). Fifty patients underwent 68Ga-PFBC01 PET/CT, including 40 with paired 18F-FDG PET/CT for head-to-head comparison. Primary outcomes included diagnostic performance (sensitivity, specificity, PPV, NPV, and inter-reader agreement). Secondary outcomes included correlations with clinical biomarkers, treatment response assessment, impact on clinical decision-making, and safety. RESULTS:68Ga-PFBC01 PET/CT demonstrated superior diagnostic performance compared with 18F-FDG PET/CT (sensitivity 96.9% vs 84.6%; specificity 71.4% vs 60.0%). Quantitative PET-derived tumor burden correlated with M protein (R = 0.325, P = 0.026), free light chains (R = 0.340-0.437, P ≤ 0.015), soluble BCMA (R = 0.433, P = 0.050), and bone marrow plasma cells (R = 0.682, P < 0.001). Imaging findings altered clinical management in multiple cases, enabling both therapy escalation and de-escalation. Blood-pool uptake strongly correlated with soluble BCMA (R = 0.899, P < 0.001) and overall disease burden (R = 0.736, P < 0.001). No serious tracer-related adverse events were observed; two patients (4%) experienced mild events. CONCLUSION:68Ga-PFBC01 PET/CT provides biologically specific, whole-body assessment of MM, outperforming 18F-FDG and enabling integrated evaluation of tumor burden and systemic disease activity, with direct implications for clinical decision-making. TRIAL REGISTRATION: CLINICALTRIALS:gov NCT06717113. FUNDING:National Natural Science Foundation of China (82472018, 82402320) to Prof. Lei Kang, 82402320 to Dr. Tianyao Wang); Beijing Nova Program (20240484725) to Prof. Lei Kang; National High Level Hospital Clinical Research Funding (Interdisciplinary Research Project of Peking University First Hospital, 2024IR07, Scientific and Technological Achievements Transformation Incubation Guidance Fund Project of Peking University First Hospital, 2025CX38, 2024CX18) to Prof. Lei Kang.

Castleman disease (CD), a rare and clinically heterogeneous condition, frequently involves renal impairment, though this relationship remains poorly characterized. This large cohort study of 183 patients (116 unicentric [UCD], 67 multicentric [MCD]) investigated renal involvement (RI). RI occurred in 6.03

This retrospective single-center cohort included 480 immunoglobulin light-chain amyloidosis (AL) and 61 light chain deposition disease (LCDD) patients from Peking University First Hospital to compare clinical profiles and outcomes. AL frequently presented with multisystem (≥ 3 organs, 31.0%) and cardiac involvement (60.8%). LCDD was kidney-dominant (eGFR < 50 mL/min/1.73m², 85.2%) with higher clonal burden (dFLC > 180mg/L, 44/60 [73.3%] with available data), a trend toward higher CR rate (65.8% vs 48.8% AL, P = 0.058), and 100% ≥ PR to daratumumab in a small subgroup (n = 11). PI-based therapy was the main backbone (66.3% vs 66.0%). LCDD had superior OS ( P < 0.001), while AL showed better renal survival in high-risk strata (albumin < 30g/L, eGFR < 50, 24h-UTP > 5g; all P < 0.05). These findings support disease-specific management: deep hematologic remission for AL and renal protection plus clone-directed therapy for LCDD.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Background and Objectives: Conventional assays for M-protein detection in multiple myeloma (MM), including serum immunofixation electrophoresis (sIFE) and serum free light-chain (sFLC) assays, have limitations in selected clinical settings. This pilot study aimed to develop and preliminarily validate a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based workflow using Kunitz trypsin inhibitor (KTI) as an internal standard for patient-specific serum M-protein light-chain tracking, particularly in low-level post-treatment samples in which conventional assays may be negative or difficult to interpret. Materials and Methods: A total of 55 serum samples from 25 patients with MM were analyzed. Serum immunoglobulin light-chain species were enriched using mixed κ/λ affinity beads, followed by reduction, KTI-based calibration, and MALDI-TOF MS analysis. Quantitative performance was evaluated using purified IgG1 κ standards. Time-matched sIFE and sFLC ratio results were used for descriptive comparison. Results: After KTI-based calibration, patient-specific M-protein light-chain molecular masses could be consistently identified. The assay showed good linearity over the range of 0.20–10.00 μg/mL, with a calibration equation of y = 6.0228x + 0.1063 and an R2 of 0.9961. The limit of detection and limit of quantification were 0.002 μg/mL and 0.008 μg/mL, respectively. Intra-day and inter-day precision were acceptable, and recovery ranged from 96.0% to 101.2%. In selected low-level or discordant samples, including cases with therapeutic interference, polyclonal background, or non-secretory disease, MALDI-TOF MS provided exploratory complementary monitoring information. Conclusions: This KTI-calibrated MALDI-TOF MS workflow showed preliminary analytical performance within the validated low-concentration range and may serve as a complementary approach for patient-specific serum M-protein light-chain monitoring in selected clinical settings of MM. Larger independent studies are required before its clinical utility can be established.

Renal involvement is an uncommon but clinically important manifestation of B-cell neoplasms, and direct comparisons between indolent and aggressive entities remain limited. This single-center retrospective biopsy-confirmed and tissue-selected study compared 28 biopsy-confirmed patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL), with 14 patients in each group, treated at Peking University First Hospital between June 2010 and June 2025. The aggressive comparator group included 13 DLBCL cases and one case annotated as HGBL with MYC and BCL2 rearrangements. Clinical features, timing of renal involvement recognition, dominant clinical entry points, pathological patterns, treatment strategies, and hematologic and renal responses were analyzed. CLL/SLL was associated with higher white blood cell and absolute lymphocyte counts, whereas DLBCL/HGBL showed higher lactate dehydrogenase and β2-microglobulin levels. The interval to renal involvement recognition was longer in CLL/SLL than in DLBCL (24.00 vs. 2.00 months, p = 0.007). At renal involvement recognition or biopsy, 24 h urinary protein excretion was nominally higher in the CLL/SLL group than in the DLBCL/HGBL group (3.90 vs. 1.58 g/24 h). CLL/SLL more often presented with proteinuria/edema, hematuria, or renal dysfunction and showed heterogeneous infiltrative lesions with concurrent glomerular or vascular involvement. DLBCL/HGBL more frequently presented with flank pain or renal mass-related manifestations and was dominated by direct infiltrative or mass-forming lesions. Treatment patterns differed markedly, whereas no significant difference in the distribution of renal responses was detected; however, this comparison was underpowered and should be interpreted descriptively. In this biopsy-confirmed, tissue-selected cohort, CLL/SLL and DLBCL/HGBL showed different observed patterns of renal involvement recognition, tissue acquisition, and renal pathological presentation. These findings support tissue-based evaluation of renal abnormalities in B-cell neoplasms but should be interpreted as descriptive and hypothesis-generating in view of the small sample size and the influence of diagnostic and biopsy pathways.

Our previous study revealed that mesenchymal stem cells (MSCs) can secrete large amounts of the chemokine CCL2 under inflammatory conditions and alleviate idiopathic pneumonia syndrome (IPS) by promoting regulatory CCR2 + CD4 + T-cell formation through the CCL2‒CCR2 axis. Given the abundance of macrophages in lung tissue, how these macrophages are regulated by MSC-based prophylaxis via IPS and their interactions with T cells in lung tissue during allo-HSCT are still not fully understood. An IPS mouse model was established, and MSC-based prophylaxis was administered. In vitro coculture systems and an IPS model were used to study the interactions among MSCs, macrophages and T cells. Prophylactic administration of MSCs induced M2 polarization and alleviated acute graft-versus-host disease (aGVHD) and lung injury in an IPS mouse model. In vitro coculture studies revealed that M2 polarization was induced by MSC-released CCL2 and that these M2 macrophages promoted the formation of regulatory CCR2 + CD4 + T cells. Blocking the CCL2-CCR2 interaction in vitro reversed MSC-induced M2 polarization and abolished the induction of CCR2 + CD4 + T-cell formation. Additionally, in vivo administration of a CCL2 or CCR2 antagonist in the IPS mouse model exacerbated aGVHD and lung injury, accompanied by a reduction in M2 macrophages and reduced formation of regulatory CCR2 + CD4 + T cells in lung tissue. MSCs alleviate IPS by facilitating M2 polarization via the CCL2‒CCR2 axis and further inducing the formation of regulatory CCR2 + CD4 + T cells.

OBJECTIVE:To screen novel diagnostic marker or therapeutic target for multiple myeloma (MM). METHODS:Sel1L, SPAG4, KCNN3 and PARM1 were identified by bioinformatics method based on GEO database as high expression genes in MM. Their RNA and protein expression levels in bone marrow mononuclear cells from myeloma cell lines U266, NCI-H929, MM.1s, RPMI8226 and leukemia cell line THP1, as well as 31 MM patients were evaluated by RT-PCR and Western blot, respectively. Meanwhile, 5 samples of bone marrow from healthy donors for allogeneic hematopoietic stem cell transplantation were employed as controls. RESULTS:Compared with leukemia cell line THP1, the expression levels of KCNN3, PARM1 and Sel1L mRNA were significantly increased in myeloma cell lines U266, NCI-H929 and MM.1s, while PARM1 was further increased in myeloma cell lines 8226. Western blot showed that the 4 genes were all expressed in the 4 myeloma cell lines. Compared with healthy controls, the expression levels of Sel1L, SPAG4, KCNN3 and PARM1 mRNA were significantly higher in MM patients (all P < 0.05). Western blot showed that the 4 genes were all expressed in MM patients, and the protein expression level of Sel1L and KCNN3 were significantly different compared with healthy donors (all P < 0.01). CONCLUSION:Sel1L, SPAG4, KCNN3 and PARM1 may be potential diagnostic markers and therapeutic targets for MM.

Objective:To screen anti-tumor drugs that improve antigen processing and presentation in acute myeloid leukemia(AML)cells.Methods:A TCR-like or TCR mimic antibody that can specifically recognize HLA-A*0201:WT1126-134(RMFPNAPYL)complex(hereafter referred to as HLA-A2:WT1)was synthesized to evaluate the function of antigen processing and presentation machinery(APM)in AML cells.AML cell line THP1 was incubated with increasing concentrations of IFN-γ,hypomethylating agents(HMA),immunomodulatory drugs(IMiD),proteasome inhibitors(PI)and γ-secretase inhibitors(GSI),followed by measuring of HLA-ABC,HLA-A2 and HLA-A2:WT1 levels by flow cytometry at consecutive time points.Results:The TCR-like antibody we generated only binds to HLA-A*0201+WT1+cells,indicating the specificity of the antibody.HLA-A2:WT1 level of THP-1 cells detected with the TCR-like antibody was increased significantly after co-incubation with IFN-γ,showing that the HLA-A2:WT1 TCR like antibody could evaluate the function of APM.Among the anti-tumor agents screened in this study,GSI(LY-411575)and HMA(decitabine and azacitidine)could significantly increase the HLA-A2:WT1 level.The IMiD lenalidomide and pomalidomide could aslo upregulate the expression of HLA-A2:WT1 complex under certain concentrations of the drugs and incubation time.As proteasome inhibitors,carfilzomib could significantly decreased the expression of HLA-A2:WT1,while bortezomib had no significant effect on HLA-A2:WT1 expression.Conclusion:HLA-A2:WT1 TCR-like antibody can effectively reflect the APM function.Some of the anti-tumor drugs can affect the APM function and immunogenicity of tumor cells.

Background Lymphocyte trafficking via chemokine receptors such as CCR5 and CXCR3 plays a critical role in the pathogenesis of aGVHD. Our previous studies showed that addition of CCR5 or CXCR3 antagonist could only slightly alleviate the development of aGVHD. Given the specificity of T lymphocytes bearing CXCR3 and CCR5, we investigated whether combined CCR5 and CXCR3 blockade could further attenuate murine aGVHD. Methods A mouse model of aGVHD was established to assess the efficacy of CCR5 or/and CXCR3 blockade on the development of aGVHD. The distribution of lymphocytes was calculated by quantification of immunostaining cells. The immunomodulatory effect on T cells were assessed by evaluating T- cell proliferation, viability, and differentiation. Results Using murine allo-HSCT model, we demonstrated that blockade of both CCR5 and CXCR3 could efficiently alleviate the development of aGVHD. Further investigation on the immune mechanisms for this prophylactic effect showed that more T cells were detained into secondary lymphoid organs (SLOs), which may lead to reduced infiltration of T cells into GVHD target organs. Our study also showed that T cells detained into SLOs dampened the activation, suppressed the polarization toward Th1 and Tc1, and induced the production of Treg cells. Conclusion These data suggest that concurrent blockade of CCR5 and CXCR3 attenuates murine aGVHD through modulating donor-derived T cell distribution and function, and this might be applicable for aGVHD prophylaxis in clinical settings.

BACKGROUND:Lymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated. METHODS:A murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined. RESULTS:CXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (p < 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (p < 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p < 0.05). CONCLUSION:This study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.

ABSTRACT A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samples of COVID-19 patients with and without hematological tumors as well as COVID-19 uninfected non-tumor individuals to obtain a comprehensive transcriptome landscape of both hematological tumor patients and non-tumor individuals. In our analysis, we further accounted for the human-SARS-CoV-2 protein interactome, human protein interactome, and human protein complex subnetworks to understand the mechanisms of SARS-CoV-2 infection and host immune responses. Our data sets enabled us to identify important SARS-CoV-2 (non-)targeted differentially expressed genes and complexes post-SARS-CoV-2 infection in both hematological tumor and non-tumor individuals. We found several unique differentially expressed genes, complexes, and functions/pathways such as blood coagulation (APOE, SERPINE1, SERPINE2, and TFPI), lipoprotein particle remodeling (APOC2, APOE, and CETP), and pro-B cell differentiation (IGHM, VPREB1, and IGLL1) during COVID-19 infection in patients with hematological tumors. In particular, APOE, a gene that is associated with both blood coagulation and lipoprotein particle remodeling, is not only upregulated in hematological tumor patients post-SARS-CoV-2 infection but also significantly expressed in acute dead patients with hematological tumors, providing clues for the design of future therapeutic strategies specifically targeting COVID-19 in patients with hematological tumors. Our data provide a rich resource for understanding the specific pathogenesis of COVID-19 in immunocompromised patients, such as those with hematological malignancies, and developing effective therapeutics for COVID-19. IMPORTANCE A majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).

Background. Fibroblastic reticular cells (FRCs) are a type of stromal cells located in the T zone in secondary lymphoid organs. Previous studies showed that FRCs possess the potential to promote myeloid differentiation. We aim to investigate whether FRCs in lymph nodes (LNs) could induce tolerogenic macrophage generation and further influence T-cell immunity at an early stage of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods. LNs were assayed to confirm the existence of proliferating macrophages after allo-HSCT. Ex vivo—expanded FRCs and bone marrow cells were cocultured to verify the generation of macrophages. Real-time quantitative PCR and ELISA assays were performed to observe the cytokines expressed by FRC. Transcriptome sequencing was performed to compare the difference between FRC-induced macrophages (FMs) and conventional macrophages. Mixed lymphocyte reaction and the utilization of FMs in acute graft-versus-host disease (aGVHD) mice were used to test the inhibitory function of FMs in T-cell immunity in vitro and in vivo. Results. We found a large number of proliferating macrophages near FRCs in LNs with tolerogenic phenotype under allo-HSCT conditions. Neutralizing anti–macrophage colony-stimulating factor receptor antibody abolished FMs generation in vitro. Phenotypic analysis and transcriptome sequencing suggested FMs possessed immunoinhibitory function. Mixed lymphocyte reaction proved that FMs could inhibit T-cell activation and differentiation toward Th1/Tc1 cells. Injection of FMs in aGVHD mice effectively attenuated aGVHD severity and mortality. Conclusions. This study has revealed a novel mechanism of immune regulation through the generation of FRC-induced tolerogenic macrophages in LNs at an early stage of allo-HSCT.

A major goal of healthy aging is to prevent declining resilience and increasing frailty, which are associated with many chronic diseases and deterioration of stress response. Here, we propose a loss-or-gain survival model, represented by the ratio of cumulative stress span to life span, to quantify stress resilience at organismal level. As a proof of concept, this is demonstrated by reduced survival resilience in Caenorhabditis elegans exposed to exogenous oxidative stress induced by paraquat or with endogenous proteotoxic stress caused by polyglutamine or amyloid-β aggregation. Based on this, we reveal that a hidden peptide ("cryptide")-AbaPep#07 (SETYELRK)-derived from abalone hemocyanin not only enhances survival resilience against paraquat-induced oxidative stress but also rescues proteotoxicity-mediated behavioral deficits in C. elegans, indicating its capacity against stress and neurodegeneration. Interestingly, AbaPep#07 is also found to increase cost-free longevity and age-related physical fitness in nematodes. We then demonstrate that AbaPep#07 can promote nuclear localization of SKN-1/Nrf, but not DAF-16/FOXO, transcription factor. In contrast to its effects in wild-type nematodes, AbaPep#07 cannot increase oxidative stress survival and physical motility in loss-of-function skn-1 mutant, suggesting an SKN-1/Nrf-dependent fashion of these effects. Further investigation reveals that AbaPep#07 can induce transcriptional activation of immune defense, lipid metabolism, and metabolic detoxification pathways, including many SKN-1/Nrf target genes. Together, our findings demonstrate that AbaPep#07 is able to boost stress resilience and reduce behavioral frailty via SKN-1/Nrf-governed transcriptional reprogramming, and provide an insight into the health-promoting potential of antioxidant cryptides as geroprotectors in aging and associated conditions.

Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied. Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed. Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III (P=0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L (P=0.011, HR=3.563), and ITE < VGPR (P=0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM. Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM.

Background 5-Hydroxymethylcytosine (5hmC), an important DNA epigenetic modification, plays a vital role in tumorigenesis, progression and prognosis in many cancers. Diffuse large B cell lymphoma (DLBCL) can involve almost any organ, but the prognosis of patients with DLBCL at different primary sites varies greatly. Previous studies have shown that 5hmC displays a tissue-specific atlas, but its role in DLBCLs at different primary sites remains unknown. Results We found that primary gastric DLBCL (PG-DLBCL) and lymph node-involved DLBCL (LN-DLBCL) patients had a favorable prognosis, while primary central nervous system DLBCL (PCNS-DLBCL) patients faced the worst prognosis, followed by primary testicular DLBCL (PT-DLBCL) and primary intestinal DLBCL (PI-DLBCL) patients. Thus, we used hmC-CATCH, a bisulfite-free and cost-effective 5hmC detection technology, to first generate the 5hmC profiles from plasma cell-free DNA (cfDNA) of DLBCL patients at these five different primary sites. Specifically, we found robust cancer-associated features that could be used to distinguish healthy individuals from DLBCL patients and distinguish among different primary sites. Through functional enrichment analysis of the differentially 5hmC-enriched genes, almost all DLBCL patients were enriched in tumor-related pathways, and DLBCL patients at different primary sites had unique characteristics. Moreover, 5hmC-based biomarkers can also highly reflect clinical features. Conclusions Collectively, we revealed the primary site differential 5hmC regions of DLBCL at different primary sites. This new strategy may help develop minimally invasive and effective methods to diagnose and determine the primary sites of DLBCL.

Abstract Castleman disease(CD) is a rare lymphoid tissue proliferative disease with an increasing focus on etiology and treatment in recent years. The consensus on CD diagnosis and treatment has been published by several organizations, playing an important role in promoting cooperation on CD managements and investigations among different teams. Based on the last 15-years retrospective real-world data from Peking University First Hospital (PKUFH), we re-classified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). 44.1% (n = 52) of UCDs in our cohort were complicated with Paraneoplastic Pemphigus (PNP). The treatment of UCD is mostly surgical resection, with a 5-year overall survival(OS) 88.1%. Patients with PNP had a poorer prognosis than those without PNP [82.9% (95% CI 123–178) vs 92.8% (95% CI 168–196), log-rank P = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143–213). In conclusion, UCDs have a better overall prognosis than MCDs. But the prognosis of those complicated with PNP was poor. Differential diagnosis of MCD is difficult. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis of MCD.

Glycosylphosphatidylinositol(GPI)-anchored transmembrane glycoprotein CD160 is a member of the immunoglobulin(Ig) superfamily(IgSF). CD160 can affect the normal function of the immune system through different effects on natural killer(NK) cells and T cells. Four isomers of CD160 have been identified, according to the presence of Ig domains and pattern anchored to cell membranes. CD160 and its ligand herpesvirus entry mediator (HVEM) form the CD160-HVEM complex, which is a particular case of direct interaction between, IgSF and tumor necrosis factor receptor super family(TNFRSF). Depending on the target cell, the CD160-HVEM complex can produce co-stimulatory or co-inhibitory signals that regulate the immune response. HVEM is also referred to as a consignaling " molecular switch" , interacting with different signaling pathways forming a network, which has a profound function in the immune system. Existing studies have shown that CD160 plays a role in various diseases including cancers, chronic viral infection diseases, autoimmune diseases, host versus graft reaction after solid organ transplantation, and other diseases. This article provides a summary of the structure, isoforms of CD160, CD160-HVEM complex, network of HVEM, and role of CD160 in human diseases.

Multiple myeloma (MM) is a malignant plasma cell disorder affecting mainly the elderly population. Revolutionary progress in immunotherapy has been made recently, including monoclonal antibodies and chimeric antigen receptor T cell (CAR-T) therapies; however, the high relapse rate remains problematic. Therefore, combination therapies against different targets would be a reasonable strategy. In this study, we present a new X-chromosome encoded testis-cancer antigen (CTA) AKAP4 as a potential target for MM. AKAP4 is expressed in MM cell lines and MM primary malignant plasma cells. HLA-A*0201-restricted cytotoxic T lymphocytes (CTLs) induced by dendritic cells (DCs) transduced with an adenovirus vector encoding the full-length AKAP4 gene were demonstrated to lyse AKAP4 + myeloma cells. Seven of the 12 candidate epitopes predicated by the BIMAS and SYFPEITH algorithms were able to bind HLA-A*0201 in the T2 binding assay, of which only two peptides were able to induce CTL cytotoxicity in the co-culture of peptide-loaded human mature dendritic cells and the autologous peripheral blood mononuclear cells (PBMCs) from the same HLA-A*0201 donor. The AKAP4 630–638 VLMLIQKLL was identified as the strongest CTL epitope by the human IFN-γ ELISPOT assay. Finally, the VLMLIQKLL-specific CTLs can lyse the HLA-A*0201 + AKAP4 + myeloma cell line U266 in vitro , and inhibit tumor growth in the mice bearing U266 tumors in vivo . These results suggest that the VLMLIQKLL epitope could be used to develop cancer vaccine or T-cell receptor transgenic T cells (TCR-T) to kill myeloma cells.