Immune System In Patients Research Articles

Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study.

This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.

Tumor-Resident Intracellular Bacteria Scavenger Activated In Situ Vaccines for Potent Cancer Photoimmunotherapy.

In situ tumor vaccines, which utilize antigens generated during tumor treatment to stimulate a cancer patient's immune system, has become a potential field in cancer immunotherapy. However, due to the immunosuppressive tumor microenvironment (ITME), the generation of tumor antigens is always mild and not sufficient. Tumor-resident intracellular bacteria have been identified as a complete tumor microenvironment component to contribute to creating ITME. Herein, a tumor-resident intracellular bacteria scavenger is designed to induce enhanced antitumor photoimmunotherapy-driven in situ vaccines for treating hypoxic tumors. This scavenger is developed by integrating photosensitizer CyI and antibiotics Doxycycline (Doxy) into thermal-sensitive tumor-derived exosomes fused liposomes (ECDL). In vitro and in vivo results showed that ECDL could homologous target to cancer cells and restrict the respiration of mitochondrial to reduce tumor hypoxia, thus providing continuous oxygen to eliminate both tumor cells and tumor-resident intracellular bacteria, which could induce in situ vaccines for ablating the primary tumor and inhibiting the tumor metastasis and recurrence. Moreover, eliminating tumor-resident intracellular bacteria neutralizes the ITME and triggers the production of bacterial-related neoantigens, which could further strength the immunotherapy. This study provided versatile and effective in situ vaccines that are promising for local, abscopal, and metastatic tumor treatment.

Glucose Metabolism Reprogramming of Immune Cells in the Microenvironment of Pancreatic and Hepatobiliary Cancers.

Pancreatic and hepatobiliary cancers are increasing in prevalence and contribute significantly to cancer-related mortality worldwide. Emerging therapeutic approaches, particularly immunotherapy, are gaining attention for their potential to harness the patient's immune system to combat these tumors. Understanding the role of immune cells in the tumor microenvironment (TME) and their metabolic reprogramming is key to developing more effective treatment strategies. This review aims to explore the relationship between immune cell function and glucose metabolism in the TME of pancreatic and hepatobiliary cancers. This review synthesizes current research on the metabolic adaptations of immune cells, specifically focusing on glucose metabolism within the TME of pancreatic and hepatobiliary cancers. We examine the mechanisms by which immune cells influence tumor progression through metabolic reprogramming and how these interactions can be targeted for therapeutic purposes. Immune cells in the TME undergo significant metabolic changes, with glucose metabolism playing a central role in modulating immune responses. These metabolic shifts not only affect immune cell function but also influence tumor behavior and progression. The unique metabolic features of immune cells in pancreatic and hepatobiliary cancers provide new opportunities for targeting immune responses to combat these malignancies more effectively. Understanding the complex relationship between immune cell glucose metabolism and tumor progression in the TME of pancreatic and hepatobiliary cancers offers promising therapeutic strategies. By modulating immune responses through targeted metabolic interventions, it may be possible to improve the efficacy of immunotherapies and better combat these aggressive cancers.

Revolutionizing Cancer Treatment: Unveiling the Power of CAR T-cell Therapy.

Cancer is a significant health challenge worldwide, causing social and economic burdens. Despite advancements in medicine, it remains a leading cause of death and is projected to increase by 2040. While conventional treatments like surgery, radiation, and chemotherapy are effective, they often have severe side effects. CAR T-cell (chimeric antigen receptor T-cell) treatment is a novel immunotherapy method personalized to the patient's immune system and directly targets cancer cells. It originated in the 1980s, and advancements have made it more effective. However, challenges remain, such as severe side effects, high costs, and manufacturing variability. Despite these challenges, the treatment with CAR T-cells has shown remarkable success, especially in hematologic malignancies. Though it is new to solid tumours, ongoing research looks promising. CAR T-cell therapy offers hope for fightingcancer, and it stands poised to redefine cancer treatment paradigms, giving renewed optimism to patients globally.

Modeling BK Virus Infection in Renal Transplant Recipients.

Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1, also known as BK virus (BKPyV). This virus attacks kidney tubule epithelial cells and is a direct threat to the health of the graft. Current standard of care in BK virus-infected transplant recipients is reduction in immunosuppressant therapy, to allow the patient's immune system to control the virus. This requires a delicate balance; immune suppression must be strong enough to prevent rejection, yet weak enough to allow viral clearance. We seek to model viral and immune dynamics with the ultimate goal of applying optimal control methods to this problem. In this paper, we begin with a previously published model and make simplifying assumptions that reduce the number of parameters from 20 to 14. We calibrate our model using newly available patient data and a detailed sensitivity analysis. Numerical results for multiple patients are given to show that the newer model reflects observed dynamics well.

Increased risk of malignancy and osteoporosis in primary Sjögren's syndrome with thyroid diseases: potential implication from T cells.

To evaluate the impact of thyroid diseases (TD) on the comorbidities incidence and immune system of patients with primary Sjögren's syndrome (pSS). A total of 329 patients diagnosed with pSS who were admitted between January 2018 and September 2023 were evaluated. The patients were divided into two groups: those with and without TD. Clinical data at the onset of SS were recorded. Kaplan-Meier method and Cox proportional hazards model were utilized for survival analysis. Flow cytometry and immunofluorescence measurements were used to analyse the lymphocyte subtypes. Of the 329 patients, 109 had TD. The most common types of TD were thyroid nodules (40.4%) and autoimmune thyroid diseases (AITD) (28.4%). Patients with TD exhibited a significantly elevated incidence risk of malignancy (14.7% vs 6.4%, p= 0.01) and osteoporosis (OP) (23.9% vs 14.1%, p= 0.03). TD comorbidity was an independent risk factor of malignancy (HR 4.7, 95% CI 1.1-19.3, p= 0.03) and OP (HR 3.7, 95% CI 1.3-10.2, p= 0.01). Patients with SS and TD exhibited a higher ratio of PD1+ subsets of total CD3+ T cells, Th and Tc-cells (all p= 0.03), as well as a lower ratio of unswitched memory B-cells (p= 0.01) in peripheral blood. The ratio of PD1+ subsets of Th-cells in salivary glands also exhibited a significantly increase in these patients compared with those without TD (p= 0.03) and the controls (p< 0.01). The incidence risk of malignancy and OP was significantly elevated in pSS patients with TD. The significant elevated proportions of PD1+ T cells may influence the occurrence of this process.

PD-L2 act as an independent immune checkpoint in colorectal cancer beyond PD-L1.

Immunotherapy, especially immune checkpoint blockade (ICB), holds promise as a therapeutic strategy in colorectal cancer (CRC) by harnessing the patient's immune system to target malignant cells. Particularly, the PD-1/PD-L1 axis is widely recognized for its critical role in tumor microenvironment immunosuppression. Antibodies targeting PD-1 or PD-L1 have shown sustained efficacy against various cancers, including CRC. Nonetheless, many CRC patients exhibit limited responses to such immunotherapy, and the resistance mechanisms remain incompletely understood. We conducted experiments with C57BL/6 mice, and used the MC38 cell line for ICB treatment studies in syngeneic mouse models. Gene and protein analyses were performed using qPCR, Western Blot, and flow cytometry, with bioinformatics for clinical data survival analysis. In this study, we reveal that targeting PD-L2 emerges as a complementary therapeutic strategy to PD-1/PD-L1 blockade in CRC. Although PD-L2 is also inducible by IFNγ, like PD-L1, it displays a unique spatial distribution within the tumor microenvironment, implying discrete roles in immune evasion. Additionally, we uncovered a significant correlation between PD-L1 and PD-L2 expression levels and the infiltration of various immune cells, encompassing multiple dendritic cell (DC) subtypes. This correlation implies an enhanced antigen presentation process that may be unleashed by blocking these two immune checkpoints. Our results highlight the significance of PD-L2 as an essential immune checkpoint alongside PD-L1 and emphasize its potential as a target for bolstering antitumor immunity in colorectal cancer.

Genomic profiles and their associations with microsatellite instability status, tumor mutational burden, and programmed death ligand 1 expression in Chinese patients with colorectal cancer.

Colorectal cancer (CRC) is among the most prevalent malignancies globally, with a rising incidence observed in younger demographics. Despite surgical resection remaining the cornerstone of treatment, metastatic CRC poses significant therapeutic challenges. Immunotherapy, a mode of treatment that leverages the patient's immune system, presents a promising frontier in CRC management, particularly for late-stage cases with limited treatment options. The study was aimed to elucidate the relationships between genetic profiles and predictive biomarkers in CRC patients to inform immunotherapy decisions and improve outcomes. We conducted a large-scale study involving 660 patients with CRC, analyzing genetic profiles and predictive biomarkers for immune checkpoint inhibitors (ICIs) using next-generation sequencing (NGS) and immunohistochemistry (IHC). The study focused on assessing the association between gene mutations and markers such as microsatellite instability (MSI) status, tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1) expression. Analysis revealed a diverse mutational landscape in CRC, with TP53 (73.64%), APC (67.58%), and KRAS (46.82%) being the most frequently mutated genes. We observed significant associations between KRAS mutations and co-occurrences with FBXW7, PIK3CA, and SMAD4 mutations, while KRAS mutations were mutually exclusive with TP53 mutations. KRAS mutations were enriched in the PD-L1 tumor proportion score (TPS) ≥1% population (P=0.03), whereas APC mutations were enriched in the PD-L1 TPS <1% population (P=0.10) as compared to their wild types. Additionally, specific mutations such as KRAS p.A146T, PIK3CA p.H1047R, and BRAF p.V600E were significantly associated with higher TMB and MSI-high status, indicating potential benefits from ICI therapy. Our findings underscore the importance of genetic profiling in guiding treatment decisions for patients with CRC, particularly in the era of immunotherapy. Understanding the complex interplay between genetic alterations and immune markers is critical for optimizing therapeutic strategies and improving clinical outcomes. Further research is warranted to validate these findings and explore personalized treatment approaches in CRC.

Identification of clonally expanded γδ T-cell populations during CAR-Tcell therapy.

Anti-CD19 Chimeric Antigen Receptor (CAR)-Tcell therapies have shown promise for treating B cell malignancies, but the clinical outcome is influenced by both the CAR-T product and the patient's immune system. The role of γδ Tcells in the context of CAR-T cell therapy remains poorly understood. This study investigates the transcriptional heterogeneity, clonal expansion and dynamics of γδ Tcells in patients undergoing anti-CD19 CAR-T cell therapy. Longitudinal single cell multi-omics analysis was performed on γδ Tcells from four patients receiving anti-CD19 CAR-T cell therapy. Single cell RNA-seq, antibody-based protein profiling (AbSeq) and full-length TCRγδ sequences revealed clonally expanded populations displaying plasticity in Tcell differentiation, and temporal dynamics of large clones, suggesting ongoing expansion and differentiation. Clonally expanded γδ Tcells had heterogeneous gene expression profiles, occupying seven transcriptionally distinct clusters. Analysis of chemokine markers indicated cluster-specific homing tendencies of circulating γδ Tcells to peripheral tissues. We found unexpectedly high frequencies of Vδ1 and Vδ3 cells in the blood with distinct gene and protein expression profiles. This analysis provides insights into the dynamic and heterogeneous nature of γδ Tcells following anti-CD19 CAR-T cell therapy, contributing valuable information for optimizing CAR-T cell therapies in B cell malignancies.

TCellR2Vec: efficient feature selection for TCR sequences for cancer classification.

Cancer remains one of the leading causes of death globally. New immunotherapies that harness the patient's immune system to fight cancer show promise, but their development requires analyzing the diversity of immune cells called T-cells. T-cells have receptors that recognize and bind to cancer cells. Sequencing these T-cell receptors allows to provide insights into their immune response, but extracting useful information is challenging. In this study, we propose a new computational method, TCellR2Vec, to select key features from T-cell receptor sequences for classifying different cancer types. We extracted features like amino acid composition, charge, and diversity measures and combined them with other sequence embedding techniques. For our experiments, we used a dataset of over 50,000 T-cell receptor sequences from five cancer types, which showed that TCellR2Vec improved classification accuracy and efficiency over baseline methods. These results demonstrate TCellR2Vec's ability to capture informative aspects of complex T-cell receptor sequences. By improving computational analysis of the immune response, TCellR2Vec could aid the development of personalized immunotherapies tailored to each patient's T-cells. This has important implications for creating more effective cancer treatments based on the individual's immune system.

Myeloid subsets impede the efficacy of anti-PD1 therapy in patients with advanced gastric cancer (WJOG10417GTR study).

Gastric cancer (GC) is one of the most common and deadly malignant diseases worldwide. Despite revolutionary advances, the therapeutic efficacy of anti-PD1/PDL1 monoclonal antibodies in advanced GC is still low due to the emergence of innate and acquired resistance to treatment. Myeloid cells represent the majority of human immune cells. Therefore, their increase, decrease, and abnormality could have a significant impact on the patient's immune system and the progression of cancer, and reprogramming, inhibiting, and eliminating the tumor-supportive types may improve the immunological situation and efficacy of immunotherapy. However, the significance of myeloid cells in anti-PD1/PDL1 therapy remains unclear in GC. In the WJOG10417GTR study on GC, we sought to identify myeloid determinants that could predict anti-PD1 therapeutic efficacy and also serve as potential therapeutic targets. We collected tumor tissues and peripheral blood from 96 patients with advanced GC before and 1 month after anti-PD1 nivolumab monotherapy, and the isolated whole leucocytes were analyzed by flow cytometry for various immune cell populations, including many myeloid subsets. Then, the relationship between the cellular levels and progression-free survival (PFS) or overall survival (OS) was statistically analyzed. We found that high levels of several myeloid subsets expressing molecules that have been targeted in drug discovery but not yet approved for clinical use were significantly associated with shorter PFS/OS as compared with low levels: PDL1+ and CTLA4+ myeloid subsets within tumors at baseline, PDL1+, B7H3+ and CD115+ myeloid subsets in peripheral blood at baseline, and LAG3+, CD155+ and CD115+ myeloid subsets in peripheral blood at post-treatment. This study revealed that these myeloid subsets are significant risk factors in nivolumab therapy for advanced GC. Targeting them may be useful as diagnostic biomarkers to predict potential anti-PD1 therapeutic efficacy, and also as therapeutic targets for accelerating the development of new drugs to improve clinical outcomes in immunotherapy for GC.

Survey on Breast Cancer analysis

Breast cancer constitutes 12% of all newly diagnosed cases globally, making it the most predominant type of cancer as a whole. Histopathology images, among all the medical image modalities, maintain the cancer's path and provide richer phenotypic relevant information. The patient's immune system is progressively predictable as a critical feature in defining the suitable treatment. Tumor-infiltrating lymphocytes (TILs), immune cells found within tumors, are emerging as key biomarkers in breast cancer. The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis.Tumoour infiltrating lymphocytes score and lymph node metastasis identification plays a very important role in staging of breast cancer.This review aims to provide a comprehensive overview on how deep learning-based method is used to compute the Tumour-Infiltrating Lymphocytes (TILs) score and lymph node metastasis from breast cancer histopathological images.

STATE OF CELLULAR IMMUNITY IN PURULENT CHOLANGITIS

Abstract. Objective: To study the state of the cellular link of immunity in acute and chronic cholangitis. Materials and methods. Cholangitis always worsens the condition of the biliary system. Depending on the magnitude of the pathological changes in the bile ducts, we distinguished three groups of patients. Group I – cholangitis caused by obstruction of the main extrahepatic bile ducts due to choledocholithiasis, group II – cholangitis in conditions of cicatricial strictures of the main bile ducts, and group III – cholangitis in conditions of already performed reconstruction of the duct system. The indicators of the cellular link of immunity were studied separately in each group. The results. The conducted studies indicate an imbalance of the immune system in patients with different courses of cholangitis. The presence of inflammation of a mild degree of severity causes stimulation of almost all links of the immune system, while the cellular branch reacts first. Conclusions. Long-term cholangitis was accompanied by suppression of the main markers of T-lymphocyte differentiation — CD2+, CD3+, CD4+ and CD8+, which take part in antigen presentation, signal transmission to other cells and affect their adhesive properties.

Revolutionizing cancer treatment: an in-depth exploration of CAR-T cell therapies.

Cancer is a leading cause of fatality worldwide. Due to the heterogeneity of cancer cells the effectiveness of various conventional cancer treatment techniques is constrained. Thus, researchers are diligently investigating therapeutic approaches like immunotherapy for effective tumor managements. Immunotherapy harnesses the inherent potential of patient's immune system to achieve desired outcomes. Within the realm of immunotherapy, CAR-T (Chimeric Antigen Receptor T) cells, emerges as a revolutionary innovation for cancer therapy. The process of CAR-T cell therapy entails extracting the patient's T cells, altering them with customized receptors designed to specifically recognize and eradicate the tumor cells, and then reinfusing the altered cells into the patient's body. Although there has been significant progress with CAR-T cell therapy in certain cases of specific B-cell leukemia and lymphoma, its effectiveness is hindered in hematological and solid tumors due to the challenges such as severe toxicities, restricted tumor infiltration, cytokine release syndrome and antigen escape. Overcoming these obstacles requires innovative approaches to design more effective CAR-T cells, which require a competent and diverse team to develop and implement. This comprehensive review addresses numerous therapeutic issues and provides a strategic solution while providing a deep understanding of the structural intricacies and production processes of CAR-T cells. In addition, this review explores the practical aspects of CAR-T cell therapy in clinical settings.

Features of immune status in patients with pulmonary tuberculosis after the COVID-19

BACKGROUND. Identification of immunological changes in patients with pulmonary tuberculosis after coronavirus infection will contribute to the prediction of its course and correction of therapeutic protocols. OBJECTIVE. The aim of the work is to determine the nature of immuno-mediated disorders caused by coronavirus disease (COVID-19) in patients with pulmonary sensitive tuberculosis (STB). MATERIALS AND METHODS. The results of a comprehensive immunological clinical and laboratory examination with subsequent computer processing of the data of 72 patients with STB of the lungs were analyzed. RESULTS. In the immune system of patients with pulmonary STB after COVID-19 the multidirectional changes are manifested by: a lower degree of increase of the blood leukocytes number (mainly due to a decrease in the absolute lymphocytes number), activation of the immune T-cells with an increase in the percent number and functional activity of pan-T-cells and T-helpers, an increase in the functional activity of T-suppressors, natural killers and killer T-cells (with the absolute and percent decrease of the latter), a higher level of the absolute and relative number of double positive (CD4+8+) cells and the functional activity of B-cells. A decrease in the level of IgA and an increase in the concentration of IgG with an decrease in the level of the medium and small circulating immune complexes, depression of the phagocytes link of immunity by reducing phagocyte number of phagocytes are observed in the blood of the patients with pulmonary STB after COVID-19. CONCLUSIONS. In the patients with pulmonary tuberculosis after COVID-19, the immune response is complex, with the crossing of immune reactions of pulmonary tuberculosis and post-COVID changes in immunity: on the one hand, previous COVID-19 promote compensatory activation of immune cells – T- and B-lymphocytes, natural killers; on the other hand, it causes suppression of antibacterial protection of mucous membranes (due to a decrease in the blood level of IgA) and reduces the body’s resistance (due to suppression of the phagocytes link of immunity).

Application of Nanomaterials in the Repair and Regeneration of Lymphatic Organs and Corresponding Biophysical Simulation Strategies

Immune system diseases, malignant tumors, and traumatic injuries can directly damage the structure and function of lymphoid organs, while subsequent radiotherapy, chemotherapy, and lymph node dissection further damage the patient's immune system, leading to immune dysfunction, metabolic disorders, and increased susceptibility to infection, which seriously affect the patient's prognosis and quality of life. In this context, nanotechnology plays a key role in lymphoid organ regeneration and immune function recovery, including improving the therapeutic effect through targeted drug delivery systems, using targeted imaging probes to achieve tumor prediction and early detection, combining nanoplatforms with immunotherapy and photodynamic therapy to achieve synergistic therapeutic effects, and using nanomaterials to regulate the tumor microenvironment to enhance the sensitivity of traditional treatments. In addition, biophysical simulation strategies that simulate the microenvironment of lymphoid organs have also attracted widespread attention, aiming to construct a native cell environment to support the regeneration and functional recovery of damaged lymphoid tissues, or to simulate immune cells to regulate lymphocytes and induce specific immune responses. The multifaceted application of nanotechnology provides promising prospects for lymphoid organ regeneration and immune system repair.

Laporan Pendidikan Kesehatan Kebutuhan Nutrisi Untuk Proses Penyembuhan Luka Post OP di Bangsal Mawar RSUD Dr Soehadi Prijonegoro Sragen

: Background: Nutrients are obtained from food and fluids which are then assimilated by the body. Nutrition itself is one of the factors that can support the wound healing process, there are things that are no less important that must be considered as well, namely the nutrients from the food we eat during the wound healing process. Objective: The purpose of postoperative diet is to strive for the patient's nutritional status to return to normal immediately to accelerate the healing process and increase the patient's immune system, by providing basic needs (fluids, energy, protein), replacing the loss of protein, glycogen, iron, and other nutrients, correcting electrolyte and fluid imbalances, preventing and stopping bleeding. Methods: The media used in health education activities is leaflets. Through leaflets we hope that the delivery of material can be understood by participants and can be delivered well.Results: The results of observations from this health education activity, that the majority of participants are active in asking questions and answering questions given by the health education team and can explain the essence of the material that has been delivered by the speaker Conclusion: Of the 20 patient families who attended 15 people had understood the fulfillment of nutritional needs for the correct post op wound healing process.

BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial

ObjectivesThis study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients...

Etiology of Leukemoid Reaction in Patients Undergoing Extracorporeal Membrane Oxygenation.

Nosocomial infections are frequent in patients receiving extracorporeal membrane oxygenation (ECMO). Leukemoid reaction, defined as >50,000 white blood cells (WBCs) per microliter, has been associated with infections in some populations. As ECMO is associated with significant inflammation activation between the patient's immune system and the circuit components, it is hypothesized that leukemoid reactions may have low specificity for identifying new infections in patients receiving ECMO. A retrospective cohort study was performed on all adult patients admitted to the Brooke Army Medical Center who received ECMO for greater than 72 hours between 2018 and 2022. Maximum WBCs were obtained for all charts. For those with leukemoid reaction, demographic information and clinical management was obtained. This study was determined to be exempt by Brooke Army Medical Center Institutional Review Board. Among 182 patients receiving ECMO for greater than 72 hours, 15 (8%) developed a leukemoid reaction while on ECMO. The median (Interquartile range, IQR) WBC was 53.94 (50.98 to 62.55). Fourteen (93%) patients underwent an infectious evaluation. Patients had a median of 2 (IQR: 2 to 3) etiologies contributing to their leukemoid reaction. At the time of leukemoid reaction, 11 (73%) patients were receiving treatment for a known infection, 6 (40%) were found to have a new thrombus, and 4 (27%) were receiving glucocorticoids. Only 1 (7%) patient was found to have a new infection, an Acinetobacter baumannii bacteremia. Leukemoid reactions occur infrequently in patients receiving ECMO and are generally multifactorial. In this cohort, leukemoid reactions rarely occurred in the setting of a new infection and suggest low utility to starting or broadening antimicrobials for these patients. Future studies identifying useful infectious markers are needed for patients receiving ECMO.

The future of immunotherapy for diffuse large B-cell lymphoma.

With the introduction of anti-CD19 chimeric antigen receptor (CAR) T-cell (CAR T) therapies, bispecific CD3/CD20 antibodies and anti-CD19 antibodies, immunotherapy continues to transform the treatment of diffuse large B-cell lymphoma (DLBCL). A number of novel immunotherapeutic strategies are under investigation to build upon current clinical benefit and offer further options to those patients who cannot tolerate conventional intensive therapies due to their age and/or state of health. Alongside immunotherapies that leverage the adaptive immune response, natural killer (NK) cell and myeloid cell-engaging therapies can utilize the innate immune system. Monoclonal antibodies engineered for greater recognition by the patient's immune system can enhance antitumor cytotoxic mechanisms mediated by NK cells and macrophages. In addition, CAR technology is extending into NK cells and macrophages and investigational immune checkpoint inhibitors targeting macrophage/myeloid cell checkpoints via the CD47/SIRPα axis are in development. Regimens that engage both innate and adaptive immune responses may help to overcome resistance to current immunotherapies. Furthermore, combinations of immunotherapy and oncogenic pathway inhibitors to reprogram the immunosuppressive tumor microenvironment of DLBCL may also potentiate antitumor responses. As immunotherapy treatment options continue to expand, both in the first-line setting and further lines of therapy, understanding how to harness these immunotherapies and the potential for combination approaches will be important for the development of future DLBCL treatment approaches.