Immunology and Immunotherapy in Critical Care: An Overview

2019 ◽  
Vol 30 (2) ◽  
pp. 113-125 ◽  
Author(s):  
Nancy Munro
Keyword(s):  
Immune Response ◽  
Critical Care ◽  
Monoclonal Antibodies ◽  
Care Setting ◽  
Checkpoint Inhibitors ◽  
Focus Of Attention ◽  
The Body ◽  
Daily Functioning ◽  
Major Focus ◽  
Cellular Therapies

Until recently, immunology was not a major focus of attention in the acute and critical care setting. With the evolution of immunotherapy, however—including the development of monoclonal antibodies, checkpoint inhibitors, and adoptive cellular therapies—an in-depth understanding of the immune system has become necessary to properly care for acutely ill patients. Lymphocytes (ie, T cells and B cells) play a major role in the daily functioning of the immune response. The interaction of these cells in protecting the body against infection and foreign substances is complicated and is the basis for many of the innovations in immunology and cancer treatment. This article explores basic immunology concepts, new drug categories, and adoptive cellular therapies that are at the forefront of cancer therapy.

scholarly journals The Mechanism of Stimulating and Mobilizing the Immune System Enhancing the Anti-Tumor Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengguo Wu ◽  
Shang Li ◽  
Xiao Zhu
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
Tumor Immunity ◽  
Checkpoint Inhibitors ◽  
The Body ◽  
Research Progress ◽  
Effective Population ◽  
Cell Components

Cancer immunotherapy is a kind of therapy that can control and eliminate tumors by restarting and maintaining the tumor-immune cycle and restoring the body’s normal anti-tumor immune response. Although immunotherapy has great potential, it is currently only applicable to patients with certain types of tumors, such as melanoma, lung cancer, and cancer with high mutation load and microsatellite instability, and even in these types of tumors, immunotherapy is not effective for all patients. In order to enhance the effectiveness of tumor immunotherapy, this article reviews the research progress of tumor microenvironment immunotherapy, and studies the mechanism of stimulating and mobilizing immune system to enhance anti-tumor immunity. In this review, we focused on immunotherapy against tumor microenvironment (TME) and discussed the important research progress. TME is the environment for the survival and development of tumor cells, which is composed of cell components and non-cell components; immunotherapy for TME by stimulating or mobilizing the immune system of the body, enhancing the anti-tumor immunity. The checkpoint inhibitors can effectively block the inhibitory immunoregulation, indirectly strengthen the anti-tumor immune response and improve the effect of immunotherapy. We also found the checkpoint inhibitors have brought great changes to the treatment model of advanced tumors, but the clinical treatment results show great individual differences. Based on the close attention to the future development trend of immunotherapy, this study summarized the latest progress of immunotherapy and pointed out a new direction. To study the mechanism of stimulating and mobilizing the immune system to enhance anti-tumor immunity can provide new opportunities for cancer treatment, expand the clinical application scope and effective population of cancer immunotherapy, and improve the survival rate of cancer patients.

scholarly journals Breast Cancer Immunotherapy: An Update

2018 ◽  
Vol 12 ◽  
pp. 117822341877480 ◽  
Author(s):  
Issam Makhoul ◽  
Mohammad Atiq ◽  
Ahmed Alwbari ◽  
Thomas Kieber-Emmons
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Cancer Surveillance ◽  
Cancer Disease ◽  
Immune Attack

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

scholarly journals Higher baseline TSH levels predict early hypothyroidism during cancer immunotherapy

2021 ◽  
Author(s):  
C. Luongo ◽  
R. Morra ◽  
C. Gambale ◽  
T. Porcelli ◽  
F. Sessa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Clinical Outcome ◽  
Adverse Events ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Thyroid Antibodies ◽  
The University ◽  
Tsh Levels

Abstract Background and purpose Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that enhance the immune response against cancer cells. ICIs are generally well tolerated, although endocrine immune-related adverse events (irAEs) are common. We investigated the risk factors for thyroid irAEs in patients treated with ICIs. Moreover, we evaluated the clinical outcome of subjects who became hypothyroid compared to euthyroid patients. Patients and methods We retrospectively analyzed a series of 195 consecutively subjects treated with ICIs for metastatic tumors at the University of Naples “Federico II” between January 2014 and March 2020. Only subjects tested for thyroid function before and during the treatment with ICIs were included. Results In the 96 patients treated with ICIs who were included [66 males, median age: 62 years (27–87)], thyroid irAEs occurred in 36 (37.5%), 16 (16.7%) a transient thyrotoxicosis, and 20 (20.8%) an hypothyroidism (in nine subjects hypothyroidism was preceded by a transient thyrotoxicosis). Only baseline TSH levels above 1.67 mIU/L and positive anti-thyroid antibodies (Ab-T) were associated with a higher risk of hypothyroidism. Patients with hypothyroidism during ICI treatment showed an improved 2-year PFS (HR = 0.82 CI 0.47–1.43; p = 0.0132) and OS (HR = 0.38 CI 95% 0.17–0.80; p = 0.011) compared to euthyroid patients. Conclusions Baseline TSH levels above 1.67 mIU/L and presence of Ab-T are risk factors for the development of thyroid irAEs. Patients affected by thyroid irAEs showed a longer survival than patients who remained euthyroid.

Magnesium metabolism: a case report and literature review

1991 ◽  
Vol 11 (5) ◽  
pp. 62-67 ◽  
Author(s):  
BA Friday ◽  
RA Reinhart
Keyword(s):  
Critical Care ◽  
Ventricular Tachycardia ◽  
Case Report ◽  
Care Setting ◽  
Clinical Manifestations ◽  
The Body ◽  
Mg Deficiency ◽  
Relationship Of ◽  
The Relationship

Magnesium has been shown to play an important role in the body. In the critical care setting of particular concern is the role of Mg++ in the treatment of malignant tachydysrhythmias such as ventricular tachycardia and ventricular fibrillation. Research is being conducted to determine appropriate methods of assessing Mg++ status, the relationship of altered Mg++ states to clinical manifestations, and the treatment of the abnormalities associated with Mg++ deficiency. Safe and effective forms of parenteral and oral Mg++ supplements are currently available.

NEUROBLASTOMA IMMUNOTHERAPY

2019 ◽  
Vol 65 (2) ◽  
pp. 181-187
Author(s):  
Aleksandr Druy ◽  
Svetlana Kuleva
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
High Risk ◽  
Checkpoint Inhibitors ◽  
Innate And Adaptive Immunity ◽  
Car T Cells ◽  
Car T ◽  
Membrane Antigens ◽  
Theoretical Evidence ◽  
Blocking Antibodies

The recent data about innate and adaptive immunity against neuroblastoma are described in the article. The era of neuroblastoma immunotherapy started since the evidence of anti-GD2 monoclonal antibodies efficiency. Nowadays monoclonal antibodies against GD2 are introduced into schemes of maintenance therapy for high-risk neuroblastoma patients. Developing of T-cells expressing chimeric antigen receptor (CAR-T cells) directed to membrane antigens is the perspective of neuroblastoma immunotherapy. PD1/PD-L1 blocking antibodies as immune checkpoint inhibitors have the theoretical evidence of potential effectiveness. Application of immunotherapeutic approaches in high-risk neuroblastoma patients together with conventional multimodal therapies requires further investigation.

Immunotherapy and potential predictive biomarkers in the treatment of neuroendocrine neoplasia

2020 ◽  
Author(s):  
Guanghui Xu ◽  
Yuhao Wang ◽  
Hushan Zhang ◽  
Xueke She ◽  
Jianjun Yang
Keyword(s):  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Predictive Biomarkers ◽  
The Body ◽  
Low Grade ◽  
Ablative Therapies ◽  
Cancer Types ◽  
New Treatment ◽  
Well Differentiated

Neuroendocrine neoplasias (NENs) are a heterogeneous group of rare tumors scattered throughout the body. Surgery, locoregional or ablative therapies as well as maintenance treatments are applied in well-differentiated, low-grade NENs, whereas cytotoxic chemotherapy is usually applied in high-grade neuroendocrine carcinomas. However, treatment options for patients with advanced or metastatic NENs are limited. Immunotherapy has provided new treatment approaches for many cancer types, including neuroendocrine tumors, but predictive biomarkers of immune checkpoint inhibitors (ICIs) in the treatment of NENs have not been fully reported. By reviewing the literature and international congress abstracts, we summarize the current knowledge of ICIs, potential predicative biomarkers in the treatment of NENs, implications and efficacy of ICIs as well as biomarkers for NENs of gastroenteropancreatic system, lung NENs and Merkel cell carcinoma in clinical practice.

scholarly journals Integration of tumor inflammation, cell proliferation, and traditional biomarkers improves prediction of immunotherapy resistance and response

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Sarabjot Pabla ◽  
R. J. Seager ◽  
Erik Van Roey ◽  
Shuang Gao ◽  
Carrie Hoefer ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Cell Activation ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Host Immune Response ◽  
Gene Signature ◽  
B Cell Activation ◽  
Rna Seq ◽  
Multiple Tumor

Abstract Background Contemporary to the rapidly evolving landscape of cancer immunotherapy is the equally changing understanding of immune tumor microenvironments (TMEs) which is crucial to the success of these therapies. Their reliance on a robust host immune response necessitates clinical grade measurements of immune TMEs at diagnosis. In this study, we describe a stable tumor immunogenic profile describing immune TMEs in multiple tumor types with ability to predict clinical benefit from immune checkpoint inhibitors (ICIs). Methods A tumor immunogenic signature (TIGS) was derived from targeted RNA-sequencing (RNA-seq) and gene expression analysis of 1323 clinical solid tumor cases spanning 35 histologies using unsupervised analysis. TIGS correlation with ICI response and survival was assessed in a retrospective cohort of NSCLC, melanoma and RCC tumor blocks, alone and combined with TMB, PD-L1 IHC and cell proliferation biomarkers. Results Unsupervised clustering of RNA-seq profiles uncovered a 161 gene signature where T cell and B cell activation, IFNg, chemokine, cytokine and interleukin pathways are over-represented. Mean expression of these genes produced three distinct TIGS score categories: strong (n = 384/1323; 29.02%), moderate (n = 354/1323; 26.76%), and weak (n = 585/1323; 44.22%). Strong TIGS tumors presented an improved ICI response rate of 37% (30/81); with highest response rate advantage occurring in NSCLC (ORR = 36.6%; 16/44; p = 0.051). Similarly, overall survival for strong TIGS tumors trended upward (median = 25 months; p = 0.19). Integrating the TIGS score categories with neoplastic influence quantified via cell proliferation showed highly proliferative and strong TIGS tumors correlate with significantly higher ICI ORR than poorly proliferative and weak TIGS tumors [14.28%; p = 0.0006]. Importantly, we noted that strong TIGS and highly [median = not achieved; p = 0.025] or moderately [median = 16.2 months; p = 0.025] proliferative tumors had significantly better survival compared to weak TIGS, highly proliferative tumors [median = 7.03 months]. Importantly, TIGS discriminates subpopulations of potential ICI responders that were considered negative for response by TMB and PD-L1. Conclusions TIGS is a comprehensive and informative measurement of immune TME that effectively characterizes host immune response to ICIs in multiple tumors. The results indicate that when combined with PD-L1, TMB and cell proliferation, TIGS provides greater context of both immune and neoplastic influences on the TME for implementation into clinical practice.

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