Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.

STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization.

Recent technological developments in spatial transcriptomics allow researchers to measure gene expression of cells and their spatial locations at the single-cell level, generating detailed biological insight into biological processes. A comprehensive database could facilitate the sharing of spatial transcriptomic data and streamline the data acquisition process for researchers. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a database that serves as a one-stop hub for spatial transcriptomics. STOmicsDB integrates 218 manually curated datasets representing 17 species. We annotated cell types, identified spatial regions and genes, and performed cell-cell interaction analysis for these datasets. STOmicsDB features a user-friendly interface for the rapid visualization of millions of cells. To further facilitate the reusability and interoperability of spatial transcriptomic data, we developed standards for spatial transcriptomic data archiving and constructed a spatial transcriptomic data archiving system. Additionally, we offer a distinctive capability of customizing dedicated sub-databases in STOmicsDB for researchers, assisting them in visualizing their spatial transcriptomic analyses. We believe that STOmicsDB could contribute to research insights in the spatial transcriptomics field, including data archiving, sharing, visualization and analysis. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.

Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees.

Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.

Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection.

Pneumococcal SP0148 and pneumolysin (Ply) derivatives are important vaccine candidates. SP0148 is a conserved lipoprotein with high immunogenicity produced by Streptococcus pneumoniae. We have previously demonstrated that SP0148 can confer protection against fatal infections caused by S. pneumoniae. ΔA146Ply is a noncytotoxic mutant of Ply that retains the TLR4 agonistic effect and has mucosal and subcutaneous adjuvant activities suggested to induce protective immunity against S. pneumoniae infection. In this study, we constructed the fusion protein ΔA146Ply-SP0148, composed of ΔA146Ply and SP0148, and evaluated the immunoprotective effect of the fusion protein. When mice were subcutaneously immunized with the fusion protein ΔA146Ply-SP0148, high levels of anti-ΔA146Ply and anti-SP0148 IgG antibodies were induced in the serum. Specific antibodies can bind to a variety of different serotypes of S. pneumoniae. Compared with mice immunized with ΔA146Ply and SP0148 alone, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 with Al(OH)3 had a higher survival rate when challenged by a lethal dose of S. pneumoniae, and they also had significantly lower lung bacterial loads and milder lung inflammation. In addition, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 stimulated strong Th1, Th2, and Th17 cell responses. In summary, these results suggest that subcutaneous immunization with the ΔA146Ply-SP0148 fusion protein can protect mice against fatal pneumococcal infection and lung infection. The fusion protein ΔA146ply-SP0148 can be a new pneumococcal vaccine target.

Cyclophosphamide desensitization in patients with severe hypersensitivity reactions to bendamustine.

INTRODUCTION: Cyclophosphamide is a nitrogen mustard alkylator employed in the treatment of many malignancies and autoimmune disorders. Despite reports of cyclophosphamide hypersensitivity ranging from rash to anaphylaxis, no cases of desensitization have been reported in the oncologic setting. CASE REPORT: We report a cyclophosphamide desensitization protocol used for two patients who experienced severe hypersensitivity to bendamustine, a structurally related drug with potential cross immunogenicity. MANAGEMENT AND OUTCOME: An interdisciplinary approach including immunologist, oncologist, and clinical pharmacists resulted in the development of a multi-step desensitization protocol for cyclophosphamide. The desensitization protocol described enabled the safe administration of cyclophosphamide for the two patients with limited treatment alternatives. DISCUSSION: To the authors' knowledge, this is the first report of cyclophosphamide desensitization in the oncologic setting. Two patients with advanced hematologic malignancies were able to receive cyclophosphamide with minimal adverse effects, despite experiencing previous severe hypersensitivity to another nitrogen mustard analogue.

Dermatomyositis associated with nivolumab therapy for melanoma: a case report and review of the literature.

We present a rare case of dermatomyositis associated with nivolumab therapy for melanoma. Nivolumab is an immune checkpoint inhibitor that blocks the programmed death-1 (PD1) receptor and has a number of associated immunotherapy related adverse events. Although most are T-cell mediated, some are antibody mediated mimics of classical autoimmune diseases. We review the characteristics of other cases of anti-PD1 associated dermatomyositis and the recent literature to better understand how to classify and treat this challenging immunotherapy related adverse event.

Formal Total Syntheses of (-)- and (+)-Actinophyllic Acid.

The formal total syntheses of (-)-actinophyllic acid and its enantiomer starting from the same chiral intermediate are reported. The synthesis features a photoredox organocatalytic asymmetric alkylation to generate the original C15 chirality, a photocatalytic C-H functionalization of 3-methylindole in flow for constructing the C16 all-carbon quaternary center, a regioselective 1,3-dipolar cycloaddition, and an intramolecular Henry reaction to assemble the pentacyclic core of the target molecule.

Schnitzler syndrome in a patient with a family history of monoclonal gammopathy.

Schnitzler syndrome is a rare disease characterized by chronic urticaria and a monoclonal gammopathy, most commonly IgM with light chains of the kappa type. There are currently no known risk factorsassociated with development of the disease. We report a case of Schnitzler syndrome in a 48-year-old man with a family history of monoclonal gammopathies. The patient's disease has been well controlled with anakinra therapy. Our case may contribute to a better understanding of the etiology of Schnitzler syndrome as his history could suggest a hereditarypredisposition for the disease. Further studies are necessary to determine whether a genetic component of Schnitzler syndrome exists, as first-degree relatives of patients with monoclonal gammopathies may be at risk for the development of the disease.

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible-Light Photoredox Catalysis.

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. A process that involves the generation of N-centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional-group tolerance.

Online Educational Tool to Promote Bone Health in Cancer Survivors.

Osteoporosis burden is significant in cancer survivors. Websites providing health information abound, but their development, quality, and source of information remain unclear. Our aim was to use a systematic and transparent approach to create an educational website on bone health, and to evaluate its potential to improve knowledge, self-management, and awareness in prostate cancer (PCa) and breast cancer (BCa) survivors. Guided by the Health Belief Model, we created a website using international standards and evaluated it in 10 PCa and 10 BCa survivors with self-administered questionnaire before, after, and 1 month after navigating the website. The mean scores on the knowledge questionnaire at baseline, postintervention and 1 month were, respectively, 5.1 (±2.0), 6.9 (±2.5), and 6.7 (±2.4), p < .008, in PCa and 3.4 (±2.7), 7.6 (±3.0), and 6.5 (±3.8), p  = .016, in BCa survivors. Acceptability ratings ranged from 60% to 100%. Participants found the website useful, helpful, and able to raise bone health awareness. Our website improved bone health knowledge in both PCa and BCa survivors. A systematic and transparent approach to the development of online educational websites could result in a tool capable of meeting the educational needs of targeted consumers. Cancer survivors could benefit from proven online educational tools.

Identification of a Novel Function of Adipocyte Plasma Membrane-Associated Protein (APMAP) in Gestational Diabetes Mellitus by Proteomic Analysis of Omental Adipose Tissue.

Gestational diabetes mellitus (GDM) is considered as an early stage of type 2 diabetes mellitus. In this study, we compared demographic and clinical data between six GDM subjects and six normal glucose tolerance (NGT; healthy controls) subjects and found that homeostasis model of assessment for insulin resistance index (HOMA-IR) increased in GDM. Many previous studies demonstrated that omental adipose tissue dysfunction could induce insulin resistance. Thus, to investigate the cause of insulin resistance in GDM, we used label-free proteomics to identify differentially expressed proteins in omental adipose tissues from GDM and NGT subjects (data are available via ProteomeXchange with identifier PXD003095). A total of 3528 proteins were identified, including 66 significantly changed proteins. Adipocyte plasma membrane-associated protein (APMAP, a.k.a. C20orf3), one of the differentially expressed proteins, was down-regulated in GDM omental adipose tissues. Furthermore, mature 3T3-L1 adipocytes were used to simulate omental adipocytes. The inhibition of APMAP expression by RNAi impaired insulin signaling and activated NFκB signaling in these adipocytes. Our study revealed that the down-regulation of APMAP in omental adipose tissue may play an important role in insulin resistance in the pathophysiology of GDM.

[Brown tumor: clinical, pathological and imaging manifestations].

OBJECTIVE: To explore the clinical, pathological characteristics and imaging manifestations of brown tumors caused by hyperparathyroidism, to improve the cognition of the disease. METHODS: The clinical, pathological characteristics and imaging manifestations of 15 cases of pathologically confirmed brown tumors were retrospectively reviewed. To analyze the imaging and pathological correlations, in addition, between the primary and secondary hyperparathyroidism led to brown tumors differential diagnoses. Rseults: In the 15 cases, aged from 26 to 66 years with median age of 51 years, 7 cases were caused by primary hyperparathyroidism, 8 cases secondary to long-term hemodialysis. Of the 15 cases(total of 34 lesions), 11 cases were multi-part bone involved. 13 of 15 patients for osteoporosis and 2 cases were osteosclerosis.32 lesions had bone destruction, 26 lesions showed expansive bone destruction, 6 showed soluble bone destruction, 12 lesions had harden edge. 23 lesions in bone destruction had calcification or ossification internal. 13 cases with soft tissue mass, enhanced significantly can be found in 3 cases. 2 lesions occured in the skull, bone density increased and the plate edge blur. pathological findings fibrous tissue , rich in blood vessels, scattered hemosiderin deposition, osteoid tissue around it. CONCLUSION: Brown tumor has relatively specific clinical history and laboratory characteristics. The imaging features include harden edge, in bone destruction has calcification or ossification internal and with soft tissue mass some enhanced significantly. The secondary brown tumor more multi-part destruction and more vertebra were involved than the primary.We can find osteosclerosis in secondary brown tumor. Those characteristic features were important to help for the diagnosis of the brown tumor.

[Effects of 5-Aza-dC on 5-Fu chemosensitivity by modulating TIP30 gene expression in human colorectal cancer cells].

OBJECTIVE: To investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on TIP30 gene expression and the relationship between TIP30 expression and the sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells. METHODS: The methylation profile of TIP30 gene in HCT116 colorectal cancer cells was determined by methylation-specific PCR. The levels of TIP30 mRNA and protein were determined by RT-PCR and Western blot after the 5-Aza-dC treatment. MTT assay was used to detect the chemosensitivity of HCT116 cells to 5-Fu. RESULTS: TIP30 gene displayed complete DNA methylation in the HCT116 cells without 5-Aza-dC pretreatment. After the 5-Aza-dC treatment for 3 days, only demethylating PCR amplification product was detected and TIP30 gene showed DNA demethylation. With the prolongation of the time of removal of 5-Aza-dC treatment, methylated and demethylated PCR amplification products were observed and TIP30 gene displayed both DNA methylation and DNA demethylation in the colorectal cancer cells. At the day 10 after removal of 5-Aza-dC, methylating PCR amplification product appeared and TIP30 gene showed DNA methylation. No expressions of TIP30 mRNA and protein were detected in the HCT116 cells untreated with 5-Aza-dC. After the treatment of 5-Aza-dC for 3 d and then removed the 5-Aza-dC, the expressions of TIP30 mRNA and protein were increased obviously. With the prolonged time after 5-Aza-dC removal, the expressions of TIP30 mRNA and protein decreased and reached the lowest level on day 10. The IC50 values of 5-Fu were 41.62, 33.17 and 4.96 µg/ml in the HCT116 cells pretreated with 5-Aza-dC, d0 and d10 with the drug removal after drug treatment for 3 d, respectively. CONCLUSIONS: The results of this study show that the expression of TIP30 gene may be associated with its DNA methylation status and may affect the sensitivity of colorectal cancer cells to 5-Fu.

T1 mapping and multimodel diffusion-weighted imaging in the assessment of cervical cancer: a preliminary study.

OBJECTIVE: To evaluate the clinical feasibility of T1 mapping and multimodel diffusion-weighted imaging (DWI) for assessing the histological type, grade, and lymphovascular space invasion (LVSI) of cervical cancer. METHODS: Eighty patients with cervical cancer and 43 patients with a normal cervix underwent T1 mapping and DWI with 11 b-values (0-2000 s/mm2). Monoexponential, biexponential, and kurtosis models were fitted to calculate the apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion (D*), perfusion fraction (f), mean diffusivity (MD), and mean kurtosis (MK). Native T1 and DWI-derived parameters (ADCmean, ADCmin, Dmean, Dmin, D*, f, MDmean, MDmin, MKmean, and MKmax) were compared based on histological type, grade, and LVSI status. RESULTS: Native T1 and DWI-derived parameters differed significantly between cervical cancer and normal cervix (all p < 0.05), except D* (p = 0.637). Native T1 and MKmean varied significantly between squamous cell carcinoma (SCC) and adenocarcinoma (both p < 0.05). ADCmin, Dmin, and MDmin were significantly lower while MKmax was significantly higher in the high-grade SCC group than in the low-grade SCC group (all p < 0.05). LVSI-positive SCC had a significantly higher MKmean than LVSI-negative SCC (p < 0.05). CONCLUSION: Both T1 mapping and multimodel DWI can effectively differentiate cervical cancer from a normal cervix and cervical adenocarcinoma from SCC. Furthermore, multimodel DWI may provide quantitative metrics for non-invasively predicting histological grade and LVSI status in SCC patients. ADVANCES IN KNOWLEDGE: Combined use of T1 mapping and multimodel DWI may provide more comprehensive information for non-invasive pre-operative evaluation of cervical cancer.

Added-value of 3D amide proton transfer MRI in assessing prognostic factors of cervical cancer: a comparative study with multiple model diffusion-weighted imaging.

Background: Amide proton transfer (APT) imaging has been gradually applied to cervical cancer, yet the relationships between APT and multiple model diffusion-weighted imaging (DWI) have yet to be investigated. This study attempted to evaluate the added value of 3-dimensional (3D) APT imaging to multiple model DWI for assessing prognostic factors of cervical cancer. Methods: This prospective diagnostic study was conducted in The First Affiliated Hospital of Zhengzhou University. A total of 88 consecutive patients with cervical cancer underwent APT imaging and DWI with 11 b-values (0-2,000 s/mm2). The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudo-diffusion (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated based on mono-exponential, bi-exponential, and kurtosis models. The mean, minimum, and maximum values of APT signal intensity (APT SI) and DWI-derived metrics were compared based on tumor stages, subtypes, grades, and lymphovascular space invasion status by Student's t-test or Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance of the parameters. Results: APT SImax, APT SImin, MKmean, and MKmax showed significant differences between adenocarcinoma (AC) and squamous cell carcinoma (SCC) (all P<0.05). APT SImean, APT SImax, and MKmax were higher and ADCmin, Dmean, Dmin, and MDmin were lower in the high-grade tumor than in low-grade tumor (all P<0.05). For distinguishing lymphovascular space invasion, only MKmean showed significant difference (P=0.010). APT SImax [odds ratio (OR) =2.347, P=0.029], APT SImin (OR =0.352; P=0.024), and MKmean (OR =6.523; P=0.001) were the independent predictors for tumor subtype, and APT SImax (OR =2.885; P=0.044), MDmin (OR =0.155, P=0.012) were the independent predictors for histological grade of cervical cancer. When APT SImin and APT SImax was combined with MKmean and MKmax, the diagnostic performance was significantly improved for differentiating AC and AC [area under the curve (AUC): 0.908, sensitivity: 87.5%; specificity: 83.3%; P<0.001]. The combination of APT SImean, APT SImax, ADCmin, MKmax, and MDmin demonstrated the highest diagnostic performance for predicting tumor grade (AUC: 0.903, sensitivity: 78.6%; specificity: 88.9%; P<0.001). Conclusions: Addition of APT to DWI may improve the ability to noninvasively predict poor prognostic factors of cervical cancer.

DegS protease regulates the motility, chemotaxis, and colonization of Vibrio cholerae.

In bacteria, DegS protease functions as an activating factor of the σE envelope stress response system, which ultimately activates the transcription of stress response genes in the cytoplasm. On the basis of high-throughput RNA sequencing, we have previously found that degS knockout inhibits the expression of flagellum synthesis- and chemotaxis-related genes, thereby indicating that DegS may be involved in the regulation of V. cholerae motility. In this study, we examined the relationships between DegS and motility in V. cholerae. Swimming motility and chemotaxis assays revealed that degS or rpoE deletion promotes a substantial reduction in the motility and chemotaxis of V. cholerae, whereas these activities were restored in ΔdegS::degS and ΔdegSΔrseA strains, indicating that DegS is partially dependent on σE to positively regulate V. cholerae activity. Gene-act network analysis revealed that the cAMP-CRP-RpoS signaling pathway, which plays an important role in flagellar synthesis, is significantly inhibited in ΔdegS mutants, whereas in response to the overexpression of cyaA/crp and rpoS in the ΔdegS strain, the motility and chemotaxis of the ΔdegS + cyaA/crp and ΔdegS + rpoS strains were partially restored compared with the ΔdegS strain. We further demonstrated that transcription levels of the flagellar regulatory gene flhF are regulated by DegS via the cAMP-CRP-RpoS signaling pathway. Overexpression of the flhF gene in the ΔdegS strain partially restored motility and chemotaxis. In addition, suckling mouse intestinal colonization experiments indicated that the ΔdegS and ΔrpoE strains were characterized by the poor colonization of mouse intestines, whereas colonization efficacy was restored in the ΔdegSΔrseA, ΔdegS + cyaA/crp, ΔdegS + rpoS, and ΔdegS + flhF strains. Collectively, our findings indicate that DegS regulates the motility and chemotaxis of V. cholerae via the cAMP-CRP-RpoS-FlhF pathway, thereby influencing the colonization of suckling mouse intestines.

DegS protease regulates antioxidant capacity and adaptability to oxidative stress environment in Vibrio cholerae.

Adaptation to oxidative stress is critical for survival of Vibrio cholerae in aquatic ecosystems and hosts. DegS activates the σE envelope stress response. We have previously revealed that DegS may be involved in regulating the oxidative stress response. In this study, we demonstrated that deletion of the degS gene attenuates the antioxidant capacity of V. cholerae. In addition, our results further revealed that the regulation of antioxidant capacity by DegS in V. cholerae could involve the cAMP-CRP complex, which regulates rpoS. XthA is an exonuclease that repairs oxidatively damaged cells and affects the bacterial antioxidant capacity. qRT-PCR showed that DegS, σE, cAMP, CRP, and RpoS positively regulate xthA gene transcription. XthA overexpression partially compensates for antioxidant deficiency in the degS mutant. These results suggest that DegS affects the antioxidant capacity of V.cholerae by regulating xthA expression via the cAMP-CRP-RpoS pathway. In a mouse intestinal colonization experiment, our data showed that V.cholerae degS, rpoE, and rpoS gene deletions were associated with significantly reduced resistance to oxidative stress and the ability to colonize the mouse intestine. In conclusion, these findings provide new insights into the regulation of antioxidant activity by V.cholerae DegS.

Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors.

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee's opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.

Selective immune suppression using interleukin-6 receptor inhibitors for management of immune-related adverse events.

BACKGROUND: Management of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs. METHODS: We performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment. RESULTS: We identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04). CONCLUSION: Targeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).